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Essentials of Osteoporosis
Dr.Hisham Abid Aldabbagh
MSc. Internal Medicine
Kingdom of Saudi Arabia
Ministry of Health
Directorate of Health
Affairs in Gurayat
Gurayat General Hospital
• Osteoporosis is the most common metabolic bone disease
in the United States and can result in devastating physical,
psychosocial, and economic consequences.
• It is often overlooked and undertreated, however, in large
part because it is clinically silent before manifesting as
fracture.
Osteoporosis. Lateral radiograph demonstrates multiple
osteoporotic vertebral compression fractures.
Kyphoplasty has been performed at one level.
• Osteoporosis, a chronic, progressive disease of
multifactorial etiology. It has been most frequently
recognized in elderly white women, although it does occur
in both sexes, all races, and all age groups. Screening at-risk
populations is essential.
• Osteoporosis is a systemic skeletal disease characterized by
low bone mass and microarchitectural deterioration of
bone tissue, with a consequent increase in bone fragility.
The disease often does not become clinically apparent until
a fracture occurs
Osteoporosis of the spine. Note the
lateral wedge fracture in L3 and the
central burst fracture in L5. The patient
had suffered a recent fall.
Osteoporosis of the spine. Observe the
considerable reduction in overall
vertebral bone density and note the
lateral wedge fracture of L2.
Pathophysiology
• Alterations in bone formation and resorption
• Estrogen deficiency
Estrogen deficiency accelerates bone loss in postmenopausal
women
• Aging
Aging is associated with a progressive decline in the supply of
osteoblasts in proportion to their demand causing bone loss.
• Calcium deficiency
Can lead to secondary hyperparathyroidism, which increases
calcium resorption from bone, decreases renal calcium excretion,
and increases renal production of 1,25-dihydroxyvitamin D
• Vitamin D deficiency
Can result in secondary hyperparathyroidism via decreased
intestinal calcium absorption.
• Osteoporotic fractures
Represent the clinical significance of derangements in bone.
• Osteoporosis versus osteomalacia
In osteoporosis, the bones are porous and brittle, whereas in
osteomalacia, the bones are soft. In osteoporosis, the mineral-to-
collagen ratio is within the reference range, whereas in
osteomalacia, the proportion of mineral composition is reduced
relative to organic material content.
• Additional factors and conditions
• Corticosteroids inhibit osteoblast function and enhance
osteoblast apoptosis.
• Polymorphisms of IL-1, IL-6 and TNF-alpha, as well as their
receptors, have been found to influence bone mass.
• Polymorphisms in the vitamin D receptor
• Alterations in insulin-like growth factor-1, bone morphogenic
protein, prostaglandin E2, nitrous oxide, and leukotrienes
• Collagen abnormalities; and leptin-related adrenergic signaling.
• Epigenetics; Prenatal and postnatal factors contribute to adult
bone mass.
Etiology
Primary Osteoporosis
Type Characteristics
Juvenile osteoporosis
Usually occurs in children or young adults of both sexes
Normal gonadal function , Age of onset: usually 8-14 years
Characteristic: abrupt bone pain and/or a fracture following trauma
Idiopathic osteoporosis
Postmenopausal
osteoporosis
(type I osteoporosis)
Occurs in women with estrogen deficiency, Characterized by a phase of
accelerated bone loss, primarily from trabecular bone
Fractures of the distal forearm and vertebral bodies are common
Age-associated or
senile osteoporosis
(type II osteoporosis)
Occurs in women and men as BMD gradually declines with aging
Represents bone loss associated with aging, Fractures occur in cortical
and trabecular bone, Wrist, vertebral, and hip fractures often seen in
patients with type II osteoporosis
Genetic/congenital
Renal hypercalciuria
Cystic fibrosis
Ehlers-Danlos syndrome
Glycogen storage disease
Gaucher disease
Marfan syndrome
Menkes steely hair syndrome
Riley-Day syndrome
Osteogenesis imperfecta
Hemochromatosis
Homocystinuria
Hypophosphatasia
Idiopathic hypercalciuria
Porphyria
Hypogonadal states
Secondary Osteoporosis in Adults
Hypogonadal states
Androgen insensitivity
Anorexia nervosa/bulimia nervosa
Female athlete triad
Hyperprolactinemia
Panhypopituitarism
Premature menopause
Turner syndrome
Klinefelter syndrome
Endocrine disorders
Cushing syndrome
Diabetes mellitus
Acromegaly
Adrenal insufficiency
Estrogen deficiency
Hyperparathyroidism
Hyperthyroidism
Hypogonadism
Pregnancy
Prolactinoma
Deficiency states
Calcium deficiency
Magnesium deficiency
Protein deficiency
Vitamin D deficiency
Bariatric surgery
Celiac disease
Gastrectomy
Malabsorption
Malnutrition
Parenteral nutrition
Primary biliary cirrhosis
Inflammatory diseases
Inflammatory bowel disease
Ankylosing spondylitis
Rheumatoid arthritis
Systemic lupus erythematosus
Hematologic and neoplastic disorders
Hemochromatosis
Hemophilia
Leukemia
Lymphoma
Multiple myeloma
Sickle cell anemia
Systemic mastocytosis
Thalassemia
Metastatic disease
Medications
Anticonvulsants
Antipsychotic drugs
Antiretroviral drugs
Aromatase inhibitors
Chemotherapeutic/transplant
drugs: cyclosporine,
tacrolimus, platinum
compounds,
cyclophosphamide,
ifosfamide, high-dose
methotrexate
Furosemide
Glucocorticoids and corticotropin
Heparin (long term)
Hormonal/endocrine therapies: gonadotropin-
releasing hormone (GnRH) agonists, luteinizing
hormone-releasing hormone (LHRH)
analogues, depomedroxyprogesterone,
excessive thyroxine
Lithium
Selective serotonin reuptake inhibitors (SSRIs)
Miscellaneous
Alcoholism
Amyloidosis
Chronic metabolic acidosis
Congestive heart failure
Depression
Emphysema
Chronic or end-stage renal disease
Chronic liver disease
HIV/AIDS
Idiopathic scoliosis
Immobility
Multiple sclerosis
Ochronosis
Organ transplantation
Pregnancy/lactation
Sarcoidosis
Weightlessness
Risk factors
Physical inactivity or immobilization
Use of certain drugs (eg,
anticonvulsants, systemic steroids,
thyroid supplements, heparin,
chemotherapeutic agents, insulin)
Alcohol and tobacco use
Androgen or estrogen deficiency
Calcium deficiency
Dowager hump
Advanced age (≥50 years)
Female sex
White or Asian ethnicity
Genetic factors, such as a family
history of osteoporosis
Thin build or small stature, eg, body
weight less than 127 lb, (57.7 kg)
Amenorrhea
Late menarche
Early menopause
Postmenopausal state
A potentially useful mnemonic for osteoporotic risk factors is
OSTEOPOROSIS, as follows:
• L O w calcium intake
• S eizure meds (anticonvulsants)
• T hin build
• E thanol intake
• Hyp O gonadism
• P revious fracture
• Thyr O id excess
• R ace (white, Asian)
• O ther relatives with osteoporosis
• S teroids
• I nactivity
• S moking
Epidemiology
• 9.9 million Americans have osteoporosis and an additional
43.1 million have low bone density.
• In the United States, two million fractures are attributed to
osteoporosis annually, with 432,000 hospital admissions,
2.5 million medical office visits and approximately 180,000
nursing home admissions.
• Globally, osteoporosis is by far the most common metabolic
bone disease, estimated to affect over 200 million people
worldwide. An estimated 75 million people in Europe, the
United States, and Japan have osteoporosis.
• Age demographics
• Risk for osteoporosis increases with age as BMD declines.
• Sex demographics
• Women are at a significantly higher risk for osteoporosis.
• Racial demographics
• Osteoporosis can occur in persons of all races and
ethnicities. In general, however, whites (especially of
northern European descent) and Asians are at increased
risk. In particular, non-Hispanic white women and Asian
women are at higher risk for osteoporosis.
Osteoporosis. Lateral radiograph of the
patient seen in the previous image following
kyphoplasty performed at 3 additional levels.
Osteoporosis. Lateral radiograph
demonstrates multiple osteoporotic
vertebral compression fractures.
Kyphoplasty has been performed at one
level.
Osteoporosis Presentation
Clinical Features
• Osteoporosis occurs in many people who have few or no
risk factors for this condition.
• Often, patients who have not sustained a fracture do not
report symptoms that would alert the clinician to suspect a
diagnosis of osteoporosis;
• Thus , this disease is a "silent thief" that generally does not
become clinically apparent until a fracture occurs.
• Screening at-risk populations is essential for proper
management of this disease and its related complications
Nonmodifiable risk factors
• Personal history of fracture as an adult
• History of fracture in a first-degree relative
• White race
• Advanced age
• Female sex
• Dementia
• Poor health or fragility
Modifiable risk factors
• Current cigarette smoking
• Low body weight (< 127 lb)
• Estrogen deficiency such as that caused by early menopause (age <
45 years) or bilateral ovariectomy and prolonged premenopausal
amenorrhea (>1 year)
• Low lifelong calcium intake
• Alcoholism
• Impaired eyesight despite adequate correction
• Recurrent falls
• Inadequate physical activity
• Poor health or frailty
Signs and symptoms
• Osteoporosis generally does not become clinically apparent until a
fracture occurs.
• Two thirds of vertebral fractures are painless.
• Typical findings in patients with painful vertebral fractures may
include the following:
- The episode of acute pain may follow a fall or minor trauma
- Pain is localized to a specific, identifiable, vertebral level in the mid
thoracic to lower thoracic or upper lumbar spine
- The pain is described variably as sharp, nagging, or dull; movement
may exacerbate pain; in some cases, pain radiates to the abdomen
- Pain is often accompanied by paravertebral muscle spasms
exacerbated by activity and decreased by lying supine
- Patients often remain motionless in bed because of fear of
causing an exacerbation of pain
- Acute pain usually resolves after 4-6 weeks; in the setting of
multiple fractures with severe kyphosis, the pain may
become chronic
Physical Examination
• The physical examination should begin with an inspection
of the patient.
• Height measurement with a stadiometer at each visit may
be useful.
• Examination of active and passive range of motion (ROM)
assists in determining whether spine, hip, wrist, or other
osseous pathology may be present.
• A thorough neurologic examination is essential to rule out
spinal cord and/or peripheral nerve compromise.
Signs of fracture
• Vertebral compression fractures may be demonstrated by a thoracic
kyphosis with an exaggerated cervical lordosis (dowager hump).
• Acute vertebral fractures may have point tenderness over the
involved vertebrae.
• Hip fractures may have severe pain with ambulation. Also may show
decreased weight-bearing on the fractured side or an antalgic gait
pattern.
• Pubic and sacral fractures may report marked pain with ambulation
and tenderness to palpation, percussion, or both.
• Signs of collagen defects
• Osteoporosis may have physical findings consistent with
the associated collagen disease
• Balance difficulties
• Osteoporosis is known to have decreased balance, possibly
secondary to differences in balance control strategies and
sway amplitude
Hip fractures occur at the upper
end of the thigh bone (femur).
Intracapsular Fracture. This
fracture occurs at the level of the
"neck" of the bone
Diagnosis
• Complete blood count: May reveal anemia
• Serum chemistry levels: Usually normal in persons with
primary osteoporosis
• Liver function tests
• Thyroid-stimulating hormone level: Thyroid dysfunction has
been associated with osteoporosis
• 25-Hydroxyvitamin D level: Vitamin D insufficiency can
predispose to osteoporosis
• Serum protein electrophoresis: Multiple myeloma may be
associated with osteoporosis
• 24 hour urine calcium/creatinine: Hypercalciuria may be
associated with osteoporosis; further investigation with
measurement of intact parathyroid hormone and urine pH
may be indicated;
• Hypocalciuria may indicate malabsorption, which should be
further evaluated with a serum vitamin D measurement
and consideration of testing for malabsorption syndromes
such as celiac sprue
• Testosterone (total and/or free) and luteinizing
hormone/follicle-stimulating hormone: Male
hypogonadism is associated with osteoporosis
Bone mineral density (BMD) measurement is recommended
in the following patients:
• Women age 65 years and older and men age 70 years and
older, regardless of clinical risk factors
• Postmenopausal women and men above age 50–69, based
on risk factor profile
• Postmenopausal women and men age 50 and older who
have had an adult-age fracture, to diagnose and determine
the degree of osteoporosis
• Vertebral imaging is recommended for the following
patients:
• All women age 70 and older and all men age 80 and older
whose BMD T-score at the spine, total hip, or femoral neck
is –1.0 or lower
• All women age 65 to 69 and all men age 70-79 whose BMD
T-score at the spine, total hip, or femoral neck is –1.5 or
lower
• Vertebral imaging is also recommended for
postmenopausal women and men age 50 and older with
the following specific risk factors:
• Low-trauma fractures
• Height loss of 1.5 inches (4 cm) or more since peak height at
age 20
• Height loss of 0.8 inches (2 cm) or more since a previously
documented height measurement
• Recent or ongoing long-term glucocorticoid treatment
• Other plain radiography features and recommended as follows:
- Obtain radiographs of the affected area in symptomatic patients
- Lateral spine radiography can be performed in asymptomatic
patients in whom a vertebral fracture is suspected; a scoliosis
series is useful for detecting occult vertebral fractures
- Radiographic findings can suggest the presence of osteopenia,
or bone loss, but cannot be used to diagnose osteoporosis
- Radiographs may also show other conditions, such as
osteoarthritis, disk disease, or spondylolisthesis
Diagnostic Considerations
• Osteomalacia
• Leukemia
• Lymphoma
• Metastases (bony and other)
• Pathologic fractures secondary to bone metastases from
cancer
• Pediatric osteogenesis imperfecta
• Renal osteodystrophy
Differential Diagnoses
• Homocystinuria/Homocysteinemia
• Hyperparathyroidism
• Imaging in Osteomalacia and Renal Osteodystrophy
• Mastocytosis
• Multiple Myeloma
• Paget Disease
• Scurvy
• Sickle Cell Anemia
Complications
• Vertebral compression fractures often occur with minimal
stress, such as coughing, lifting, or bending.
• Hip fractures are the most devastating and occur most
commonly at the femoral neck and intertrochanteric regions.
• Secondary complications of hip fractures include nosocomial
infections and pulmonary thromboembolism.
• Increased morbidity and mortality secondary to vertebral
compression fractures and hip fractures.
• Spinal deformities and a dowager's hump, and they may lose
1-2 inches of height by their seventh decade of life
Prognosis
The prognosis for osteoporosis is good if bone loss is
detected in the early phases and proper intervention is
undertaken.
• Effect of fractures on prognosis
- Vertebral compression fractures are associated with
increased morbidity and mortality rates.
- Hip fractures, More than 250,000 hip fractures are
attributed to osteoporosis each year, they are associated
with significantly increased morbidity and mortality rates in
men and women.
Osteoporosis Workup
Approach Considerations
• Laboratory studies to establish baseline values and to look
for potential secondary causes of osteoporosis
• Measurement of bone mineral density (BMD) to assess
bone loss and estimate the risk of fracture
• Bone biopsy may be indicated in specific situations.
Laboratory Studies
CBC results may reveal anemia, as in sickle cell disease, and may
raise the suspicion for alcohol abuse
Calcium levels can reflect underlying disease states
levels of serum calcium, phosphate, and alkaline phosphatase are
usually normal in persons with primary osteoporosis,
although alkaline phosphatase levels may be elevated after a
fracture
Creatinine levels may decrease with increasing parathyroid
hormone (PTH) levels or may be elevated in patients with
multiple myeloma
Creatinine levels are also used to estimate creatinine clearance,
which may indicate reduced renal function in elderly patients
Magnesium is very important in calcium homeostasis; decreased
levels of magnesium may affect calcium absorption and
metabolism
Increased levels of alanine aminotransferase (ALT), aspartate
aminotransferase (AST), gamma-glutamyl transferase (GGT),
bilirubin, and alkaline phosphatase may indicate alcohol abuse
Thyroid dysfunction has been associated with osteoporosis
and should therefore be ruled out
Vitamin D level to assess vitamin D insufficiency;
inadequate vitamin D levels can predispose persons to
osteoporosis
Disorder
Tests for Secondary
Causes of Osteoporosis
This study assesses for hypercalciuria and
hypocalciuria
24-Hour urine calcium
level
An intact PTH result is essential in ruling out
hyperparathyroidism; an elevated PTH level may
be present in benign familial hypocalciuric
hypercalcemia
Parathyroid hormone
(PTH) level
Reflect the status of thyroid glandTFT
Evaluate a sex hormone deficiency
as a secondary cause of osteoporosis
Testosterone and gonadotropin
levels
To exclude Cushing syndrome,a
urine free cortisol value or overnight
dexamethasone suppression test
Urinary free cortisol level and tests
for adrenal hypersecretion
To identify multiple myeloma
Serum protein electrophoresis
(SPEP) and urine protein
electrophoresis (UPEP)
Can help identify celiac disease
Antigliadin
antiendomysial antibodies
Help identify mastocytosis
Serum tryptase
urine N-methylhistamine
When a hematologic disorder is
suspected
Bone marrow biopsy
• Biochemical Markers of Bone Turnover
• Biochemical markers of bone turnover reflect bone
formation or bone resorption.
• These markers (both formation and resorption) may be
elevated in high-bone-turnover states (eg, early
postmenopausal osteoporosis) and may be useful in some
patients for monitoring early response to therapy.
A summary list of Biochemical Markers of Bone Turnover
Bone resorption markersBone formation markers
Urinary hydroxyproline
Urinary total pyridinoline
Urinary free deoxypyridinoline
Urinary collagen type 1
Urinary or serum collagen type 1
Bone sialoprotein
Tartrate-resistant acid phosphatase
Serum total alkaline phosphtase
Serum bone–specific alkaline
phosphatase
Serum osteocalcin
Serum type 1 procollagen
Plain Radiography
• .
Plain radiography is
recommended to assess
overall skeletal integrity.
In particular, in the workup
for osteoporosis, plain
radiography may be
indicated if a fracture is
already suspected or if
patients have lost more
than 1.5 inches of height Asymmetric loss in vertebral
body height with kyphosis
Lateral spine radiography can be
performed in asymptomatic
patients in whom a vertebral
fracture is suspected, in those
with height loss in the absence of
other symptoms, or in those with
pain in the thoracic or upper
lumbar spine .
A scoliosis series is useful for
detecting occult vertebral
fractures.
Severe osteoporosis.
multiple vertebral crush fractures
• Radiographic findings can suggest the presence of
osteopenia, or bone loss, but cannot be used to diagnose
osteoporosis.
• Osteopenia is suggested by a cortical width that is less than
the medullary width.
• Plain radiography is not as accurate as BMD testing.
Because osteoporosis predominantly affects trabecular
bone rather than cortical bone, radiography does not reveal
osteoporotic changes until they affect the cortical bone.
Intertrochanteric Fracture.
This occurs further down the bone
Subtrochanteric Fracture. This occurs
even further down the bone and may be
broken into several pieces.
Dual-Energy X-Ray Absorptiometry (DXA)
DXA is currently
the criterion
standard for the
evaluation of
BMD.
DXA is used to
calculate BMD
at the lumbar
spine, hip, and
proximal femur
• DXA provides the patient’s T-score, which is the BMD value
compared with that of control subjects who are at their peak
BMD.
• World Health Organization (WHO) criteria define a normal T-
score value as within 1 standard deviation (SD) of the mean
BMD value in a healthy young adult.
• Values lying farther from the mean are stratified as follows:
- T-score of –1 to –2.5 SD indicates osteopenia
- T-score of less than –2.5 SD indicates osteoporosis
- T-score of less than –2.5 SD with fragility fracture(s) indicates
severe osteoporosis
• DXA also provides the patient’s Z-score, which reflects a value
compared with that of persons matched for age and sex.
• Z-scores adjusted for ethnicity or race should be used in the
following patients:
• Premenopausal women
• Men younger than 50 years
• Children
• Z-score values of –2.0 SD or lower are defined as "below the
expected range for age" and those above –2.0 SD as "within the
expected range for age." The diagnosis of osteoporosis in these
groups should not be based on densitometric criteria alone.
WHO Definition of Osteoporosis Based on BMD Measurements by DXA
Definition Bone Mass Density Measurement T-Score
Normal
BMD within 1 SD of the mean bone
density for young adult women
T-score ≥ –1
Low bone mass
(osteopenia)
BMD 1–2.5 SD below the mean for
young-adult women
T-score between –1
and –2.5
Osteoporosis
BMD ≥2.5 SD below the normal mean
for young-adult women
T-score ≤ –2.5
Severe or
“established”
osteoporosis
BMD ≥2.5 SD below the normal mean
for young-adult women in a patient
who has already experienced ≥1
fractures
T-score ≤ –2.5 (with
fragility fracture[s])
FRAX tool
• The Fracture Risk Assessment (FRAX) tool, accessible to
healthcare providers and patients, is a validated instrument
used to estimate 10-year risks for fractures, including those
for black, Asian, and Hispanic women A 65-year-old white
woman with no other risk factors has a 9.3% 10-year risk
for any osteoporotic fracture.
• Generally, estimated fracture risks in nonwhite women are
lower than those for white women of the same age.
Quantitative Computed Tomography
• Quantitative computed tomography (QCT) is another
method employed to measure spinal BMD. At the spine, it
measures BMD as a true volume density in g/cm3, which is
not influenced by bone size. This technique can be used in
both adults and children.
• QCT scanning of the spine is the most sensitive method for
diagnosing osteoporosis, because it measures trabecular
bone within the vertebral body. At the hip, QCT produces
DXA-equivalent T-scores and BMD measures in g/cm2.
Single-Photon Emission CT
• Single-photon emission computed tomography (SPECT)
scanning represents a tomographic (CT-like) bone imaging
technique that offers better image contrast and more
accurate lesion localization than planar bone scanning.
• It increases the sensitivity and specificity of bone scanning
for detection of lumbar spine lesions by 20-50% over planar
techniques
Quantitative Ultrasonography
• Quantitative ultrasonography (QUS) of the calcaneus is a
low-cost portable screening tool. It has the advantage of
not involving radiation, but it is not as accurate as other
imaging methods.
• Ultrasonography cannot be used for monitoring skeletal
changes over time, nor can it be used to monitor the
response to treatment, because of its lack of precision.
Magnetic Resonance Imaging
• Magnetic resonance imaging (MRI) may be useful in
identifying fractures and in the assessment of metabolic
bone disease.
• Using fat-suppression sequences, marrow edema consistent
with fracture may be noted as areas of hypointensity on T1-
weighted images in association with corresponding areas of
hyperintensity on T2-weighted images.
• MRI is a very sensitive modality and is believed by some to
be the diagnostic imaging method of choice in the
detection of acute fractures, such as sacral fractures
An MRI may identify a hip fracture otherwise missed on plain X-ray.
Bone Scanning
• Bone scanning assesses the function and tissue metabolism
of organs by using a radionuclide (technetium-99m [99m Tc])
that emits radiation in proportion to its attachment to a
target structure.
• This technique detects an increase in osteoblastic activity
(as seen in compression fractures).
Bone Biopsy and Histologic Features
• Bone biopsy can help to exclude underlying pathologic
conditions, such as multiple myeloma, that may be
responsible for presumed osteoporotic fracture.
• Typically, iliac crest biopsy is performed either in the minor
procedure suite or in the operating room.
Osteoporosis Management
Approach Considerations
• Preventive measures include modification of general
lifestyle factors, such as increasing weight-bearing and
muscle-strengthening exercise, which have been linked to
fractures in epidemiologic studies, and ensuring optimum
calcium and vitamin D intake as adjunct to active
antifracture therapy.
• Medical care includes the administration of adequate
calcium, vitamin D, and anti-osteoporotic medication such
as bisphosphonates, parathyroid hormone (PTH),
raloxifene, and estrogen. In addition, potentially treatable
underlying causes of osteoporosis such as
hyperparathyroidism and hyperthyroidism should be ruled
out or treated if detected.
• Surgical care includes vertebroplasty and kyphoplasty,
which are minimally invasive spine procedures used for the
management of painful osteoporotic vertebral compression
fractures. However, there may be an increased risk of
adjacent level vertebral fractures after these procedures.
• The first goal of rehabilitation in osteoporosis patients is to
control pain if a fracture has occurred.
• Spinal compression fractures can be extremely painful and
can cause short- and long-term morbidity.
• Oral analgesics on a regular schedule can be implemented.
Pain-relieving modalities such as moist hot packs and
transcutaneous electrical nerve stimulation should also be
considered.
Pharmacologic Therapy
• Currently, no treatment can completely reverse established
osteoporosis.
• Early intervention can prevent osteoporosis in most people.
• For patients with established osteoporosis, medical
intervention can halt its progression.
• If secondary osteoporosis is present, treatment for the
primary disorder should be provided.
• Therapy should be individualized based on each patient’s
clinical scenario, with the risks and benefits of treatment
discussed between the clinician and patient.
Pharmacologic therapy should be reserved for
postmenopausal women and men aged 50 years or older
who present with the following:
• A hip or vertebral fracture (vertebral fractures may be clinical
or morphometric [ie, identified on a radiograph alone])
• T-score of –2.5 or less at the femoral neck or spine after
appropriate evaluation to exclude secondary causes
• Low bone mass (T-score between –1.0 and –2.5 at the femoral
neck or spine) and a 10-year probability of a hip fracture of 3%
or greater or a 10-year probability of a major osteoporosis-
related fracture of 20% or greater
• The agents currently available for osteoporosis treatment—
all of which should be accompanied by sufficient intake of
calcium and vitamin D—include the following:
• Bisphosphonates
• Raloxifene
• Calcitonin
• Denosumab
• Teriparatide (recombinant human parathyroid hormone)
The National Osteoporosis Guideline Group (NOGG) guidelines
2013 on the diagnosis and management of osteoporosis in men
and postmenopausal women, aged 50 years or older:
• Pharmacotherapies shown to lower the risk for vertebral
fracture (and for hip fracture in some cases) include
bisphosphonates, denosumab, parathyroid hormone peptides,
raloxifene, and strontium ranelate
• Generic alendronate is usually first-line treatment because of
its broad spectrum of anti-fracture efficacy and low cost
• Ibandronate, risedronate, zoledronic acid, denosumab,
raloxifene, or strontium ranelate may be appropriate therapy
if alendronate is contraindicated or poorly tolerated
• Because of their high cost, parathyroid hormone peptides
should be used only for patients at very high risk, especially
for vertebral fractures
• Postmenopausal women may benefit from calcitriol,
etidronate, and hormone replacement therapy
• Treatments for men at increased fracture risk include
alendronate, risedronate, zoledronic acid, and teriparatide
• Patients at increased risk for fracture should start
alendronate or other bone-protective treatment when
beginning glucocorticoid therapy
• For postmenopausal women, pharmacotherapy for
prevention and treatment of glucocorticoid-induced
osteoporosis includes alendronate, etidronate, and
risedronate; treatment options for both sexes are
teriparatide and zoledronic acid
• Calcium and vitamin D supplementation is widely
recommended for older persons who are housebound or
live in residential or nursing homes and is often
recommended as an adjunct to other treatments for
osteoporosis
• Potential adverse cardiovascular effects of calcium
supplementation are controversial, but it may be prudent
to increase dietary calcium intake and use vitamin D alone
rather than using both calcium and vitamin D
supplementation
• Withdrawal of bisphosphonate treatment is associated with
decreases in BMD and bone turnover after 2-3 years for
alendronate and 1-2 years for ibandronate and risedronate
• Continuation of bisphosphonates without the need for
further evaluation is recommended for high-risk
individuals; when bisphosphonates are continued,
treatment review, including renal function evaluation, is
needed every 5 years
• If bisphosphonates are discontinued, fracture risk should be
reevaluated after every new fracture, or after 2 years if no
new fracture occurs
• After 3 years of zoledronic acid treatment, the benefits on
BMD density persist for at least another 3 years after
discontinuation; most patients should stop treatment after
3 years, and their physician should review the need for
continuation of therapy 3 years later
• Treatment review is recommended after 5 years for
alendronate, risedronate, or ibandronate and after 3 years
for zoledronic acid
• Persons with a previous vertebral fracture or a
pretreatment hip BMD T-score of -2.5 SD or less may be at
increased risk for vertebral fracture if zoledronic acid is
discontinued
Bisphosphonates
• Bisphosphonates are the most commonly used agents for
osteoporosis. They have been employed for both treatment and
prevention. Oral and intravenous options are available.
• Alendronate (Fosamax) is approved for the treatment of
osteoporosis in men, in postmenopausal women, and in
patients with glucocorticoid-induced osteoporosis. It has been
shown to increase spinal and hip mineral density in
postmenopausal women.
• Well-conducted controlled clinical trials indicate that
alendronate reduces the rate of fracture at the spine, hip, and
wrist by 50% in patients with osteoporosis.
• The treatment dose of alendronate is 70 mg/wk, to be taken
sitting upright with a large glass of water at least 30 minutes
before eating in the morning. Alendronate is also available in
combination with cholecalciferol (vitamin D3).
• The combination alendronate/vitamin D3 (Fosamax Plus D) is
indicated for the treatment of osteoporosis in men to increase
bone mass.
• Other oral bisphosphonates include risedronate (Actonel) or
risedronate delayed-release (Atelvia), given daily, weekly, or
monthly. It is also available as a combination product with
calcium as risedronate/calcium carbonate (Actonel with
Calcium).
• Ibandronate (Boniva) is another bisphosphonate that can be
given orally once a month. Intravenous bisphosphonates are
excellent choices for patients intolerant of oral bisphosphonates
or for those in whom adherence is an issue. Ibandronate is also
available as an intravenous formulation that is given every 3
months. Ibandronate has not shown efficacy in nonvertebral
fractures in clinical trials.
• Zoledronic acid (Reclast) is the most potent bisphosphonate
available.
• Zoledronic acid is a once-yearly intravenous infusion approved
for the treatment of osteoporosis in men, in postmenopausal
women, and in patients with glucocorticoid-induced
osteoporosis.
Guidelines on long-term bisphosphonate treatment
recommendations In 2016 :
• After 5 years of oral bisphosphonates or 3 years of intravenous
bisphosphonates, reassessment of risk should be considered.
• In women at high risk (eg, older women, those with a low hip
T-score or high fracture risk score, those with previous major
osteoporotic fracture, or those who fracture on therapy),
continuation of treatment for up to 10 years (oral) or 6 years
(intravenous), with periodic evaluation, should be considered.
•
• The risk of atypical femoral fracture, clearly increases with
the duration of bisphosphonate therapy
• For women not at high fracture risk, a drug holiday of 2 to 3
years can be considered after 3 to 5 years of BP treatment.
Selective estrogen receptor modulators
• Selective estrogen receptor modulators (SERMs) are
considered to provide the beneficial effects of estrogen
without the potentially adverse outcomes.
• Raloxifene (Evista) is a SERM indicated for the treatment
and prevention of osteoporosis in postmenopausal women.
The usual dose is 60 mg given orally daily.
• It can also be given in combination with calcium and
vitamin D. It is the first SERM studied for breast cancer
prevention, and it decreases bone resorption through
actions on estrogen receptors.
Parathyroid hormone
• Teriparatide (Forteo) is a recombinant human parathyroid
hormone (1-34) (PTH [1-34]) and is the only available
anabolic agent for the treatment of osteoporosis.
• It is indicated for the treatment of women with
postmenopausal osteoporosis who are at high risk of
fracture, who have been intolerant of previous osteoporosis
therapy, or in whom osteoporosis treatment has failed to
increase bone mass.
• It is indicated in men with idiopathic or hypogonadal
osteoporosis who are at high risk of fracture, who have
been intolerant of previous osteoporosis therapy, or in
whom osteoporosis therapy has failed.
• Teriparatide is also approved for the treatment of patients
with glucocorticoid-induced osteoporosis.
• Before treatment with teriparatide, levels of serum calcium,
PTH, and 25(OH)D need to be monitored.
Calcitonin
• Calcitonin-salmon (Fortical, Miacalcin) is a hormone that
decreases osteoclast activity, thereby impeding
postmenopausal bone loss.
• It is indicated for the treatment of women who are more
than 5 years post menopause and have low bone mass
relative to healthy premenopausal women.
• Calcitonin-salmon should be reserved for patients who
refuse or cannot tolerate estrogens or in whom estrogens
are contraindicated.
• It is recommended in conjunction with adequate calcium
and vitamin D intake to prevent the progressive loss of
bone mass.
• It is available as an injection and as an intranasal spray.
• The intranasal spray is delivered as a single daily spray that
provides 200 IU of the drug.
• The drug can be delivered subcutaneously, but this route is
rarely used.
Denosumab
• Denosumab (Prolia) is a humanized monoclonal antibody
directed against the receptor activator of the nuclear
factor-kappa B ligand (RANKL), which is a key mediator of
the resorptive phase of bone remodeling.
• It decreases bone resorption by inhibiting osteoclast
activity.
• It is indicated to increase bone mass in men and
postmenopausal women with osteoporosis who are at high
risk of fracture, have multiple risk factors for fracture, are
intolerant to other available osteoporosis therapies, or in
whom osteoporosis therapies have failed. .
• Because the overactivity of RANKL is a major factor in bone
loss in patients with autoimmune and inflammatory
disorders, such as ulcerative colitis, denosumab may
become first-line therapy for these patients.
• Denosumab in combination with teriparatide has been
shown to increase BMD more than either drug alone.
Hormone replacement therapy
• Hormone replacement therapy (HRT) was once considered
a first-line therapy for the prevention and treatment of
osteoporosis in women.
• Although HRT is not currently recommended for the
treatment of osteoporosis, it is important to mention
because many osteoporosis patients in a typical practice
still use it for controlling postmenopausal symptoms.
• Other agents
• Strontium ranelate is approved for the treatment of
osteoporosis in some countries in Europe. It reduces the
risk of both spine and nonvertebral fractures.
Vertebroplasty and Kyphoplasty
• Operative interventions include anterior and posterior
decompression and stabilization with placement of such
internal fixation devices as screws, plates, cages, or rods.
Bone grafting is routinely performed to achieve bony union.
The failure rate of spinal arthrodesis is significant because
achieving adequate fixation of hardware in osteoporotic
bone is difficult. Moreover, patients who are elderly have a
reduced osteogenic potential.
• Vertebroplasty and balloon kyphoplasty are indicated in
patients with incapacitating and persistent severe focal
back pain related to vertebral collapse.
Dietary Measures
• Adequate calcium and vitamin D intake are important in
persons of any age, particularly in childhood as the bones
are maturing, and are essential in the prevention and
treatment of osteoporosis.
• Vitamin D is increasingly being recognized as a key element
in overall bone health, calcium absorption, balance (eg,
reduction in risk of falls and muscle performance.
• Patients who ingest inadequate amounts of vitamin D and
calcium should receive oral supplementation.
Physical and Occupational Therapy
• Physical therapy
- Physical therapy focuses on improving a patient's strength,
flexibility, posture, and balance to prevent falls and maximize
physical function.
- Postural retraining is key in this population. Spinal bone
mineral density (BMD) is directly correlated with the
strength of the back extensors; therefore, maintaining and
strengthening the back extensors should be emphasized.
Occupational therapy
• Training in the performance of activities of daily living
(ADLs) and in the proper use of adaptive equipment are
essential to the prevention of future falls.
• Home modification focuses on reducing the risk of falling by
installing handrails and grab bars in hallways, stairs, and
bathrooms.
• The use of a shower chair, tub bench, and adaptive bathing
devices also can be beneficial.
• The application of nonskid tape to steps (indoors and
outdoors), as well as the removal of throw rugs, greatly
improves home safety.
Exercise
• Aerobic low-impact exercises, such as walking and bicycling,
generally are recommended. During these activities, ensure
that the patient maintains an upright spinal alignment.
• Proper therapy for osteoporosis includes 3-5 sessions per week
of weight-bearing exercises, such as walking or jogging, with
each session lasting 45-60 minutes. The patient should be
instructed in a home-exercise program that incorporates the
necessary elements for improving posture and overall physical
fitness.
• The physical therapist must address balance training, because
fall prevention is important in eliminating the complication of
fracture.
Prevention of Osteoporosis
• Primary prevention of osteoporosis starts in childhood.
Patients require adequate calcium intake, vitamin D intake, and
weight-bearing exercise. Beyond this, prevention of
osteoporosis has two components: behavior modification and
pharmacologic interventions.
• The following behaviors should be modified to reduce the risk
of developing osteoporosis:
- Cigarette smoking
- Physical inactivity
- Intake of alcohol, caffeine, sodium, animal protein, and calcium
Consultations
• The most important consultation is with a rheumatologist
or an endocrinologist.
• These specialists can help obtain the proper laboratory
tests and imaging studies needed to rule out causes of
secondary osteoporosis.
• In patients with uncontrolled pain that does not respond to
conventional therapies, an invasive pain specialist may be
consulted for proper interventional procedures
• Consultation with a spine surgeon is appropriate for
patients with intractable, severe, function-limiting
symptomatology that has not been relieved by
noninterventional techniques.
• Consultation with a nonsurgical spine specialist is
appropriate for a patient who is not a surgical candidate or
whose symptoms persist despite surgical fixation
Patient Education
• Patient education is paramount in the treatment of
osteoporosis.
• Many patients are unaware of the serious consequences of
osteoporosis, including increased morbidity and mortality,
and only become concerned when osteoporosis manifests
in the form of fracture; accordingly, it is important to
educate them regarding these consequences.
• Early prevention and treatment are essential in the
appropriate management of osteoporosis.
Thanks for Your Interest in
preventing osteoporosis
Email: dr.hishamdabbagh@gmail.com
Email: haldabag@moh.gov.sa
Mobile: 00966536715868

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Osteoporosis

  • 1. Essentials of Osteoporosis Dr.Hisham Abid Aldabbagh MSc. Internal Medicine Kingdom of Saudi Arabia Ministry of Health Directorate of Health Affairs in Gurayat Gurayat General Hospital
  • 2. • Osteoporosis is the most common metabolic bone disease in the United States and can result in devastating physical, psychosocial, and economic consequences. • It is often overlooked and undertreated, however, in large part because it is clinically silent before manifesting as fracture.
  • 3. Osteoporosis. Lateral radiograph demonstrates multiple osteoporotic vertebral compression fractures. Kyphoplasty has been performed at one level.
  • 4. • Osteoporosis, a chronic, progressive disease of multifactorial etiology. It has been most frequently recognized in elderly white women, although it does occur in both sexes, all races, and all age groups. Screening at-risk populations is essential. • Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility. The disease often does not become clinically apparent until a fracture occurs
  • 5. Osteoporosis of the spine. Note the lateral wedge fracture in L3 and the central burst fracture in L5. The patient had suffered a recent fall. Osteoporosis of the spine. Observe the considerable reduction in overall vertebral bone density and note the lateral wedge fracture of L2.
  • 6.
  • 7. Pathophysiology • Alterations in bone formation and resorption • Estrogen deficiency Estrogen deficiency accelerates bone loss in postmenopausal women • Aging Aging is associated with a progressive decline in the supply of osteoblasts in proportion to their demand causing bone loss. • Calcium deficiency Can lead to secondary hyperparathyroidism, which increases calcium resorption from bone, decreases renal calcium excretion, and increases renal production of 1,25-dihydroxyvitamin D
  • 8. • Vitamin D deficiency Can result in secondary hyperparathyroidism via decreased intestinal calcium absorption. • Osteoporotic fractures Represent the clinical significance of derangements in bone. • Osteoporosis versus osteomalacia In osteoporosis, the bones are porous and brittle, whereas in osteomalacia, the bones are soft. In osteoporosis, the mineral-to- collagen ratio is within the reference range, whereas in osteomalacia, the proportion of mineral composition is reduced relative to organic material content.
  • 9. • Additional factors and conditions • Corticosteroids inhibit osteoblast function and enhance osteoblast apoptosis. • Polymorphisms of IL-1, IL-6 and TNF-alpha, as well as their receptors, have been found to influence bone mass. • Polymorphisms in the vitamin D receptor • Alterations in insulin-like growth factor-1, bone morphogenic protein, prostaglandin E2, nitrous oxide, and leukotrienes • Collagen abnormalities; and leptin-related adrenergic signaling. • Epigenetics; Prenatal and postnatal factors contribute to adult bone mass.
  • 10. Etiology Primary Osteoporosis Type Characteristics Juvenile osteoporosis Usually occurs in children or young adults of both sexes Normal gonadal function , Age of onset: usually 8-14 years Characteristic: abrupt bone pain and/or a fracture following trauma Idiopathic osteoporosis Postmenopausal osteoporosis (type I osteoporosis) Occurs in women with estrogen deficiency, Characterized by a phase of accelerated bone loss, primarily from trabecular bone Fractures of the distal forearm and vertebral bodies are common Age-associated or senile osteoporosis (type II osteoporosis) Occurs in women and men as BMD gradually declines with aging Represents bone loss associated with aging, Fractures occur in cortical and trabecular bone, Wrist, vertebral, and hip fractures often seen in patients with type II osteoporosis
  • 11. Genetic/congenital Renal hypercalciuria Cystic fibrosis Ehlers-Danlos syndrome Glycogen storage disease Gaucher disease Marfan syndrome Menkes steely hair syndrome Riley-Day syndrome Osteogenesis imperfecta Hemochromatosis Homocystinuria Hypophosphatasia Idiopathic hypercalciuria Porphyria Hypogonadal states Secondary Osteoporosis in Adults
  • 12. Hypogonadal states Androgen insensitivity Anorexia nervosa/bulimia nervosa Female athlete triad Hyperprolactinemia Panhypopituitarism Premature menopause Turner syndrome Klinefelter syndrome Endocrine disorders Cushing syndrome Diabetes mellitus Acromegaly Adrenal insufficiency Estrogen deficiency Hyperparathyroidism Hyperthyroidism Hypogonadism Pregnancy Prolactinoma
  • 13. Deficiency states Calcium deficiency Magnesium deficiency Protein deficiency Vitamin D deficiency Bariatric surgery Celiac disease Gastrectomy Malabsorption Malnutrition Parenteral nutrition Primary biliary cirrhosis Inflammatory diseases Inflammatory bowel disease Ankylosing spondylitis Rheumatoid arthritis Systemic lupus erythematosus
  • 14. Hematologic and neoplastic disorders Hemochromatosis Hemophilia Leukemia Lymphoma Multiple myeloma Sickle cell anemia Systemic mastocytosis Thalassemia Metastatic disease
  • 15. Medications Anticonvulsants Antipsychotic drugs Antiretroviral drugs Aromatase inhibitors Chemotherapeutic/transplant drugs: cyclosporine, tacrolimus, platinum compounds, cyclophosphamide, ifosfamide, high-dose methotrexate Furosemide Glucocorticoids and corticotropin Heparin (long term) Hormonal/endocrine therapies: gonadotropin- releasing hormone (GnRH) agonists, luteinizing hormone-releasing hormone (LHRH) analogues, depomedroxyprogesterone, excessive thyroxine Lithium Selective serotonin reuptake inhibitors (SSRIs)
  • 16. Miscellaneous Alcoholism Amyloidosis Chronic metabolic acidosis Congestive heart failure Depression Emphysema Chronic or end-stage renal disease Chronic liver disease HIV/AIDS Idiopathic scoliosis Immobility Multiple sclerosis Ochronosis Organ transplantation Pregnancy/lactation Sarcoidosis Weightlessness
  • 17. Risk factors Physical inactivity or immobilization Use of certain drugs (eg, anticonvulsants, systemic steroids, thyroid supplements, heparin, chemotherapeutic agents, insulin) Alcohol and tobacco use Androgen or estrogen deficiency Calcium deficiency Dowager hump Advanced age (≥50 years) Female sex White or Asian ethnicity Genetic factors, such as a family history of osteoporosis Thin build or small stature, eg, body weight less than 127 lb, (57.7 kg) Amenorrhea Late menarche Early menopause Postmenopausal state
  • 18. A potentially useful mnemonic for osteoporotic risk factors is OSTEOPOROSIS, as follows: • L O w calcium intake • S eizure meds (anticonvulsants) • T hin build • E thanol intake • Hyp O gonadism • P revious fracture • Thyr O id excess • R ace (white, Asian) • O ther relatives with osteoporosis • S teroids • I nactivity • S moking
  • 19. Epidemiology • 9.9 million Americans have osteoporosis and an additional 43.1 million have low bone density. • In the United States, two million fractures are attributed to osteoporosis annually, with 432,000 hospital admissions, 2.5 million medical office visits and approximately 180,000 nursing home admissions. • Globally, osteoporosis is by far the most common metabolic bone disease, estimated to affect over 200 million people worldwide. An estimated 75 million people in Europe, the United States, and Japan have osteoporosis.
  • 20. • Age demographics • Risk for osteoporosis increases with age as BMD declines. • Sex demographics • Women are at a significantly higher risk for osteoporosis. • Racial demographics • Osteoporosis can occur in persons of all races and ethnicities. In general, however, whites (especially of northern European descent) and Asians are at increased risk. In particular, non-Hispanic white women and Asian women are at higher risk for osteoporosis.
  • 21. Osteoporosis. Lateral radiograph of the patient seen in the previous image following kyphoplasty performed at 3 additional levels. Osteoporosis. Lateral radiograph demonstrates multiple osteoporotic vertebral compression fractures. Kyphoplasty has been performed at one level.
  • 22.
  • 24. Clinical Features • Osteoporosis occurs in many people who have few or no risk factors for this condition. • Often, patients who have not sustained a fracture do not report symptoms that would alert the clinician to suspect a diagnosis of osteoporosis; • Thus , this disease is a "silent thief" that generally does not become clinically apparent until a fracture occurs. • Screening at-risk populations is essential for proper management of this disease and its related complications
  • 25.
  • 26. Nonmodifiable risk factors • Personal history of fracture as an adult • History of fracture in a first-degree relative • White race • Advanced age • Female sex • Dementia • Poor health or fragility
  • 27. Modifiable risk factors • Current cigarette smoking • Low body weight (< 127 lb) • Estrogen deficiency such as that caused by early menopause (age < 45 years) or bilateral ovariectomy and prolonged premenopausal amenorrhea (>1 year) • Low lifelong calcium intake • Alcoholism • Impaired eyesight despite adequate correction • Recurrent falls • Inadequate physical activity • Poor health or frailty
  • 28.
  • 29. Signs and symptoms • Osteoporosis generally does not become clinically apparent until a fracture occurs. • Two thirds of vertebral fractures are painless. • Typical findings in patients with painful vertebral fractures may include the following: - The episode of acute pain may follow a fall or minor trauma - Pain is localized to a specific, identifiable, vertebral level in the mid thoracic to lower thoracic or upper lumbar spine - The pain is described variably as sharp, nagging, or dull; movement may exacerbate pain; in some cases, pain radiates to the abdomen
  • 30. - Pain is often accompanied by paravertebral muscle spasms exacerbated by activity and decreased by lying supine - Patients often remain motionless in bed because of fear of causing an exacerbation of pain - Acute pain usually resolves after 4-6 weeks; in the setting of multiple fractures with severe kyphosis, the pain may become chronic
  • 31. Physical Examination • The physical examination should begin with an inspection of the patient. • Height measurement with a stadiometer at each visit may be useful. • Examination of active and passive range of motion (ROM) assists in determining whether spine, hip, wrist, or other osseous pathology may be present. • A thorough neurologic examination is essential to rule out spinal cord and/or peripheral nerve compromise.
  • 32. Signs of fracture • Vertebral compression fractures may be demonstrated by a thoracic kyphosis with an exaggerated cervical lordosis (dowager hump). • Acute vertebral fractures may have point tenderness over the involved vertebrae. • Hip fractures may have severe pain with ambulation. Also may show decreased weight-bearing on the fractured side or an antalgic gait pattern. • Pubic and sacral fractures may report marked pain with ambulation and tenderness to palpation, percussion, or both.
  • 33. • Signs of collagen defects • Osteoporosis may have physical findings consistent with the associated collagen disease • Balance difficulties • Osteoporosis is known to have decreased balance, possibly secondary to differences in balance control strategies and sway amplitude
  • 34. Hip fractures occur at the upper end of the thigh bone (femur). Intracapsular Fracture. This fracture occurs at the level of the "neck" of the bone
  • 35. Diagnosis • Complete blood count: May reveal anemia • Serum chemistry levels: Usually normal in persons with primary osteoporosis • Liver function tests • Thyroid-stimulating hormone level: Thyroid dysfunction has been associated with osteoporosis • 25-Hydroxyvitamin D level: Vitamin D insufficiency can predispose to osteoporosis • Serum protein electrophoresis: Multiple myeloma may be associated with osteoporosis
  • 36. • 24 hour urine calcium/creatinine: Hypercalciuria may be associated with osteoporosis; further investigation with measurement of intact parathyroid hormone and urine pH may be indicated; • Hypocalciuria may indicate malabsorption, which should be further evaluated with a serum vitamin D measurement and consideration of testing for malabsorption syndromes such as celiac sprue • Testosterone (total and/or free) and luteinizing hormone/follicle-stimulating hormone: Male hypogonadism is associated with osteoporosis
  • 37. Bone mineral density (BMD) measurement is recommended in the following patients: • Women age 65 years and older and men age 70 years and older, regardless of clinical risk factors • Postmenopausal women and men above age 50–69, based on risk factor profile • Postmenopausal women and men age 50 and older who have had an adult-age fracture, to diagnose and determine the degree of osteoporosis
  • 38. • Vertebral imaging is recommended for the following patients: • All women age 70 and older and all men age 80 and older whose BMD T-score at the spine, total hip, or femoral neck is –1.0 or lower • All women age 65 to 69 and all men age 70-79 whose BMD T-score at the spine, total hip, or femoral neck is –1.5 or lower
  • 39. • Vertebral imaging is also recommended for postmenopausal women and men age 50 and older with the following specific risk factors: • Low-trauma fractures • Height loss of 1.5 inches (4 cm) or more since peak height at age 20 • Height loss of 0.8 inches (2 cm) or more since a previously documented height measurement • Recent or ongoing long-term glucocorticoid treatment
  • 40. • Other plain radiography features and recommended as follows: - Obtain radiographs of the affected area in symptomatic patients - Lateral spine radiography can be performed in asymptomatic patients in whom a vertebral fracture is suspected; a scoliosis series is useful for detecting occult vertebral fractures - Radiographic findings can suggest the presence of osteopenia, or bone loss, but cannot be used to diagnose osteoporosis - Radiographs may also show other conditions, such as osteoarthritis, disk disease, or spondylolisthesis
  • 41. Diagnostic Considerations • Osteomalacia • Leukemia • Lymphoma • Metastases (bony and other) • Pathologic fractures secondary to bone metastases from cancer • Pediatric osteogenesis imperfecta • Renal osteodystrophy
  • 42. Differential Diagnoses • Homocystinuria/Homocysteinemia • Hyperparathyroidism • Imaging in Osteomalacia and Renal Osteodystrophy • Mastocytosis • Multiple Myeloma • Paget Disease • Scurvy • Sickle Cell Anemia
  • 43. Complications • Vertebral compression fractures often occur with minimal stress, such as coughing, lifting, or bending. • Hip fractures are the most devastating and occur most commonly at the femoral neck and intertrochanteric regions. • Secondary complications of hip fractures include nosocomial infections and pulmonary thromboembolism. • Increased morbidity and mortality secondary to vertebral compression fractures and hip fractures. • Spinal deformities and a dowager's hump, and they may lose 1-2 inches of height by their seventh decade of life
  • 44. Prognosis The prognosis for osteoporosis is good if bone loss is detected in the early phases and proper intervention is undertaken. • Effect of fractures on prognosis - Vertebral compression fractures are associated with increased morbidity and mortality rates. - Hip fractures, More than 250,000 hip fractures are attributed to osteoporosis each year, they are associated with significantly increased morbidity and mortality rates in men and women.
  • 46. Approach Considerations • Laboratory studies to establish baseline values and to look for potential secondary causes of osteoporosis • Measurement of bone mineral density (BMD) to assess bone loss and estimate the risk of fracture • Bone biopsy may be indicated in specific situations.
  • 47. Laboratory Studies CBC results may reveal anemia, as in sickle cell disease, and may raise the suspicion for alcohol abuse Calcium levels can reflect underlying disease states levels of serum calcium, phosphate, and alkaline phosphatase are usually normal in persons with primary osteoporosis, although alkaline phosphatase levels may be elevated after a fracture
  • 48. Creatinine levels may decrease with increasing parathyroid hormone (PTH) levels or may be elevated in patients with multiple myeloma Creatinine levels are also used to estimate creatinine clearance, which may indicate reduced renal function in elderly patients Magnesium is very important in calcium homeostasis; decreased levels of magnesium may affect calcium absorption and metabolism Increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin, and alkaline phosphatase may indicate alcohol abuse
  • 49. Thyroid dysfunction has been associated with osteoporosis and should therefore be ruled out Vitamin D level to assess vitamin D insufficiency; inadequate vitamin D levels can predispose persons to osteoporosis
  • 50. Disorder Tests for Secondary Causes of Osteoporosis This study assesses for hypercalciuria and hypocalciuria 24-Hour urine calcium level An intact PTH result is essential in ruling out hyperparathyroidism; an elevated PTH level may be present in benign familial hypocalciuric hypercalcemia Parathyroid hormone (PTH) level Reflect the status of thyroid glandTFT
  • 51. Evaluate a sex hormone deficiency as a secondary cause of osteoporosis Testosterone and gonadotropin levels To exclude Cushing syndrome,a urine free cortisol value or overnight dexamethasone suppression test Urinary free cortisol level and tests for adrenal hypersecretion To identify multiple myeloma Serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP)
  • 52. Can help identify celiac disease Antigliadin antiendomysial antibodies Help identify mastocytosis Serum tryptase urine N-methylhistamine When a hematologic disorder is suspected Bone marrow biopsy
  • 53. • Biochemical Markers of Bone Turnover • Biochemical markers of bone turnover reflect bone formation or bone resorption. • These markers (both formation and resorption) may be elevated in high-bone-turnover states (eg, early postmenopausal osteoporosis) and may be useful in some patients for monitoring early response to therapy.
  • 54. A summary list of Biochemical Markers of Bone Turnover Bone resorption markersBone formation markers Urinary hydroxyproline Urinary total pyridinoline Urinary free deoxypyridinoline Urinary collagen type 1 Urinary or serum collagen type 1 Bone sialoprotein Tartrate-resistant acid phosphatase Serum total alkaline phosphtase Serum bone–specific alkaline phosphatase Serum osteocalcin Serum type 1 procollagen
  • 55. Plain Radiography • . Plain radiography is recommended to assess overall skeletal integrity. In particular, in the workup for osteoporosis, plain radiography may be indicated if a fracture is already suspected or if patients have lost more than 1.5 inches of height Asymmetric loss in vertebral body height with kyphosis
  • 56. Lateral spine radiography can be performed in asymptomatic patients in whom a vertebral fracture is suspected, in those with height loss in the absence of other symptoms, or in those with pain in the thoracic or upper lumbar spine . A scoliosis series is useful for detecting occult vertebral fractures. Severe osteoporosis. multiple vertebral crush fractures
  • 57. • Radiographic findings can suggest the presence of osteopenia, or bone loss, but cannot be used to diagnose osteoporosis. • Osteopenia is suggested by a cortical width that is less than the medullary width.
  • 58. • Plain radiography is not as accurate as BMD testing. Because osteoporosis predominantly affects trabecular bone rather than cortical bone, radiography does not reveal osteoporotic changes until they affect the cortical bone.
  • 59. Intertrochanteric Fracture. This occurs further down the bone Subtrochanteric Fracture. This occurs even further down the bone and may be broken into several pieces.
  • 60. Dual-Energy X-Ray Absorptiometry (DXA) DXA is currently the criterion standard for the evaluation of BMD. DXA is used to calculate BMD at the lumbar spine, hip, and proximal femur
  • 61. • DXA provides the patient’s T-score, which is the BMD value compared with that of control subjects who are at their peak BMD. • World Health Organization (WHO) criteria define a normal T- score value as within 1 standard deviation (SD) of the mean BMD value in a healthy young adult. • Values lying farther from the mean are stratified as follows: - T-score of –1 to –2.5 SD indicates osteopenia - T-score of less than –2.5 SD indicates osteoporosis - T-score of less than –2.5 SD with fragility fracture(s) indicates severe osteoporosis
  • 62. • DXA also provides the patient’s Z-score, which reflects a value compared with that of persons matched for age and sex. • Z-scores adjusted for ethnicity or race should be used in the following patients: • Premenopausal women • Men younger than 50 years • Children • Z-score values of –2.0 SD or lower are defined as "below the expected range for age" and those above –2.0 SD as "within the expected range for age." The diagnosis of osteoporosis in these groups should not be based on densitometric criteria alone.
  • 63. WHO Definition of Osteoporosis Based on BMD Measurements by DXA Definition Bone Mass Density Measurement T-Score Normal BMD within 1 SD of the mean bone density for young adult women T-score ≥ –1 Low bone mass (osteopenia) BMD 1–2.5 SD below the mean for young-adult women T-score between –1 and –2.5 Osteoporosis BMD ≥2.5 SD below the normal mean for young-adult women T-score ≤ –2.5 Severe or “established” osteoporosis BMD ≥2.5 SD below the normal mean for young-adult women in a patient who has already experienced ≥1 fractures T-score ≤ –2.5 (with fragility fracture[s])
  • 64. FRAX tool • The Fracture Risk Assessment (FRAX) tool, accessible to healthcare providers and patients, is a validated instrument used to estimate 10-year risks for fractures, including those for black, Asian, and Hispanic women A 65-year-old white woman with no other risk factors has a 9.3% 10-year risk for any osteoporotic fracture. • Generally, estimated fracture risks in nonwhite women are lower than those for white women of the same age.
  • 65. Quantitative Computed Tomography • Quantitative computed tomography (QCT) is another method employed to measure spinal BMD. At the spine, it measures BMD as a true volume density in g/cm3, which is not influenced by bone size. This technique can be used in both adults and children. • QCT scanning of the spine is the most sensitive method for diagnosing osteoporosis, because it measures trabecular bone within the vertebral body. At the hip, QCT produces DXA-equivalent T-scores and BMD measures in g/cm2.
  • 66. Single-Photon Emission CT • Single-photon emission computed tomography (SPECT) scanning represents a tomographic (CT-like) bone imaging technique that offers better image contrast and more accurate lesion localization than planar bone scanning. • It increases the sensitivity and specificity of bone scanning for detection of lumbar spine lesions by 20-50% over planar techniques
  • 67. Quantitative Ultrasonography • Quantitative ultrasonography (QUS) of the calcaneus is a low-cost portable screening tool. It has the advantage of not involving radiation, but it is not as accurate as other imaging methods. • Ultrasonography cannot be used for monitoring skeletal changes over time, nor can it be used to monitor the response to treatment, because of its lack of precision.
  • 68. Magnetic Resonance Imaging • Magnetic resonance imaging (MRI) may be useful in identifying fractures and in the assessment of metabolic bone disease. • Using fat-suppression sequences, marrow edema consistent with fracture may be noted as areas of hypointensity on T1- weighted images in association with corresponding areas of hyperintensity on T2-weighted images. • MRI is a very sensitive modality and is believed by some to be the diagnostic imaging method of choice in the detection of acute fractures, such as sacral fractures
  • 69. An MRI may identify a hip fracture otherwise missed on plain X-ray.
  • 70. Bone Scanning • Bone scanning assesses the function and tissue metabolism of organs by using a radionuclide (technetium-99m [99m Tc]) that emits radiation in proportion to its attachment to a target structure. • This technique detects an increase in osteoblastic activity (as seen in compression fractures).
  • 71. Bone Biopsy and Histologic Features • Bone biopsy can help to exclude underlying pathologic conditions, such as multiple myeloma, that may be responsible for presumed osteoporotic fracture. • Typically, iliac crest biopsy is performed either in the minor procedure suite or in the operating room.
  • 73. Approach Considerations • Preventive measures include modification of general lifestyle factors, such as increasing weight-bearing and muscle-strengthening exercise, which have been linked to fractures in epidemiologic studies, and ensuring optimum calcium and vitamin D intake as adjunct to active antifracture therapy.
  • 74. • Medical care includes the administration of adequate calcium, vitamin D, and anti-osteoporotic medication such as bisphosphonates, parathyroid hormone (PTH), raloxifene, and estrogen. In addition, potentially treatable underlying causes of osteoporosis such as hyperparathyroidism and hyperthyroidism should be ruled out or treated if detected.
  • 75. • Surgical care includes vertebroplasty and kyphoplasty, which are minimally invasive spine procedures used for the management of painful osteoporotic vertebral compression fractures. However, there may be an increased risk of adjacent level vertebral fractures after these procedures.
  • 76. • The first goal of rehabilitation in osteoporosis patients is to control pain if a fracture has occurred. • Spinal compression fractures can be extremely painful and can cause short- and long-term morbidity. • Oral analgesics on a regular schedule can be implemented. Pain-relieving modalities such as moist hot packs and transcutaneous electrical nerve stimulation should also be considered.
  • 77. Pharmacologic Therapy • Currently, no treatment can completely reverse established osteoporosis. • Early intervention can prevent osteoporosis in most people. • For patients with established osteoporosis, medical intervention can halt its progression. • If secondary osteoporosis is present, treatment for the primary disorder should be provided. • Therapy should be individualized based on each patient’s clinical scenario, with the risks and benefits of treatment discussed between the clinician and patient.
  • 78. Pharmacologic therapy should be reserved for postmenopausal women and men aged 50 years or older who present with the following: • A hip or vertebral fracture (vertebral fractures may be clinical or morphometric [ie, identified on a radiograph alone]) • T-score of –2.5 or less at the femoral neck or spine after appropriate evaluation to exclude secondary causes • Low bone mass (T-score between –1.0 and –2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture of 3% or greater or a 10-year probability of a major osteoporosis- related fracture of 20% or greater
  • 79. • The agents currently available for osteoporosis treatment— all of which should be accompanied by sufficient intake of calcium and vitamin D—include the following: • Bisphosphonates • Raloxifene • Calcitonin • Denosumab • Teriparatide (recombinant human parathyroid hormone)
  • 80. The National Osteoporosis Guideline Group (NOGG) guidelines 2013 on the diagnosis and management of osteoporosis in men and postmenopausal women, aged 50 years or older: • Pharmacotherapies shown to lower the risk for vertebral fracture (and for hip fracture in some cases) include bisphosphonates, denosumab, parathyroid hormone peptides, raloxifene, and strontium ranelate • Generic alendronate is usually first-line treatment because of its broad spectrum of anti-fracture efficacy and low cost • Ibandronate, risedronate, zoledronic acid, denosumab, raloxifene, or strontium ranelate may be appropriate therapy if alendronate is contraindicated or poorly tolerated
  • 81. • Because of their high cost, parathyroid hormone peptides should be used only for patients at very high risk, especially for vertebral fractures • Postmenopausal women may benefit from calcitriol, etidronate, and hormone replacement therapy • Treatments for men at increased fracture risk include alendronate, risedronate, zoledronic acid, and teriparatide • Patients at increased risk for fracture should start alendronate or other bone-protective treatment when beginning glucocorticoid therapy
  • 82. • For postmenopausal women, pharmacotherapy for prevention and treatment of glucocorticoid-induced osteoporosis includes alendronate, etidronate, and risedronate; treatment options for both sexes are teriparatide and zoledronic acid • Calcium and vitamin D supplementation is widely recommended for older persons who are housebound or live in residential or nursing homes and is often recommended as an adjunct to other treatments for osteoporosis
  • 83. • Potential adverse cardiovascular effects of calcium supplementation are controversial, but it may be prudent to increase dietary calcium intake and use vitamin D alone rather than using both calcium and vitamin D supplementation • Withdrawal of bisphosphonate treatment is associated with decreases in BMD and bone turnover after 2-3 years for alendronate and 1-2 years for ibandronate and risedronate
  • 84. • Continuation of bisphosphonates without the need for further evaluation is recommended for high-risk individuals; when bisphosphonates are continued, treatment review, including renal function evaluation, is needed every 5 years • If bisphosphonates are discontinued, fracture risk should be reevaluated after every new fracture, or after 2 years if no new fracture occurs
  • 85. • After 3 years of zoledronic acid treatment, the benefits on BMD density persist for at least another 3 years after discontinuation; most patients should stop treatment after 3 years, and their physician should review the need for continuation of therapy 3 years later • Treatment review is recommended after 5 years for alendronate, risedronate, or ibandronate and after 3 years for zoledronic acid • Persons with a previous vertebral fracture or a pretreatment hip BMD T-score of -2.5 SD or less may be at increased risk for vertebral fracture if zoledronic acid is discontinued
  • 86. Bisphosphonates • Bisphosphonates are the most commonly used agents for osteoporosis. They have been employed for both treatment and prevention. Oral and intravenous options are available. • Alendronate (Fosamax) is approved for the treatment of osteoporosis in men, in postmenopausal women, and in patients with glucocorticoid-induced osteoporosis. It has been shown to increase spinal and hip mineral density in postmenopausal women. • Well-conducted controlled clinical trials indicate that alendronate reduces the rate of fracture at the spine, hip, and wrist by 50% in patients with osteoporosis.
  • 87. • The treatment dose of alendronate is 70 mg/wk, to be taken sitting upright with a large glass of water at least 30 minutes before eating in the morning. Alendronate is also available in combination with cholecalciferol (vitamin D3). • The combination alendronate/vitamin D3 (Fosamax Plus D) is indicated for the treatment of osteoporosis in men to increase bone mass. • Other oral bisphosphonates include risedronate (Actonel) or risedronate delayed-release (Atelvia), given daily, weekly, or monthly. It is also available as a combination product with calcium as risedronate/calcium carbonate (Actonel with Calcium).
  • 88. • Ibandronate (Boniva) is another bisphosphonate that can be given orally once a month. Intravenous bisphosphonates are excellent choices for patients intolerant of oral bisphosphonates or for those in whom adherence is an issue. Ibandronate is also available as an intravenous formulation that is given every 3 months. Ibandronate has not shown efficacy in nonvertebral fractures in clinical trials. • Zoledronic acid (Reclast) is the most potent bisphosphonate available. • Zoledronic acid is a once-yearly intravenous infusion approved for the treatment of osteoporosis in men, in postmenopausal women, and in patients with glucocorticoid-induced osteoporosis.
  • 89. Guidelines on long-term bisphosphonate treatment recommendations In 2016 : • After 5 years of oral bisphosphonates or 3 years of intravenous bisphosphonates, reassessment of risk should be considered. • In women at high risk (eg, older women, those with a low hip T-score or high fracture risk score, those with previous major osteoporotic fracture, or those who fracture on therapy), continuation of treatment for up to 10 years (oral) or 6 years (intravenous), with periodic evaluation, should be considered. •
  • 90. • The risk of atypical femoral fracture, clearly increases with the duration of bisphosphonate therapy • For women not at high fracture risk, a drug holiday of 2 to 3 years can be considered after 3 to 5 years of BP treatment.
  • 91. Selective estrogen receptor modulators • Selective estrogen receptor modulators (SERMs) are considered to provide the beneficial effects of estrogen without the potentially adverse outcomes. • Raloxifene (Evista) is a SERM indicated for the treatment and prevention of osteoporosis in postmenopausal women. The usual dose is 60 mg given orally daily. • It can also be given in combination with calcium and vitamin D. It is the first SERM studied for breast cancer prevention, and it decreases bone resorption through actions on estrogen receptors.
  • 92. Parathyroid hormone • Teriparatide (Forteo) is a recombinant human parathyroid hormone (1-34) (PTH [1-34]) and is the only available anabolic agent for the treatment of osteoporosis. • It is indicated for the treatment of women with postmenopausal osteoporosis who are at high risk of fracture, who have been intolerant of previous osteoporosis therapy, or in whom osteoporosis treatment has failed to increase bone mass.
  • 93. • It is indicated in men with idiopathic or hypogonadal osteoporosis who are at high risk of fracture, who have been intolerant of previous osteoporosis therapy, or in whom osteoporosis therapy has failed. • Teriparatide is also approved for the treatment of patients with glucocorticoid-induced osteoporosis. • Before treatment with teriparatide, levels of serum calcium, PTH, and 25(OH)D need to be monitored.
  • 94. Calcitonin • Calcitonin-salmon (Fortical, Miacalcin) is a hormone that decreases osteoclast activity, thereby impeding postmenopausal bone loss. • It is indicated for the treatment of women who are more than 5 years post menopause and have low bone mass relative to healthy premenopausal women. • Calcitonin-salmon should be reserved for patients who refuse or cannot tolerate estrogens or in whom estrogens are contraindicated.
  • 95. • It is recommended in conjunction with adequate calcium and vitamin D intake to prevent the progressive loss of bone mass. • It is available as an injection and as an intranasal spray. • The intranasal spray is delivered as a single daily spray that provides 200 IU of the drug. • The drug can be delivered subcutaneously, but this route is rarely used.
  • 96. Denosumab • Denosumab (Prolia) is a humanized monoclonal antibody directed against the receptor activator of the nuclear factor-kappa B ligand (RANKL), which is a key mediator of the resorptive phase of bone remodeling. • It decreases bone resorption by inhibiting osteoclast activity. • It is indicated to increase bone mass in men and postmenopausal women with osteoporosis who are at high risk of fracture, have multiple risk factors for fracture, are intolerant to other available osteoporosis therapies, or in whom osteoporosis therapies have failed. .
  • 97. • Because the overactivity of RANKL is a major factor in bone loss in patients with autoimmune and inflammatory disorders, such as ulcerative colitis, denosumab may become first-line therapy for these patients. • Denosumab in combination with teriparatide has been shown to increase BMD more than either drug alone.
  • 98. Hormone replacement therapy • Hormone replacement therapy (HRT) was once considered a first-line therapy for the prevention and treatment of osteoporosis in women. • Although HRT is not currently recommended for the treatment of osteoporosis, it is important to mention because many osteoporosis patients in a typical practice still use it for controlling postmenopausal symptoms.
  • 99. • Other agents • Strontium ranelate is approved for the treatment of osteoporosis in some countries in Europe. It reduces the risk of both spine and nonvertebral fractures.
  • 100. Vertebroplasty and Kyphoplasty • Operative interventions include anterior and posterior decompression and stabilization with placement of such internal fixation devices as screws, plates, cages, or rods. Bone grafting is routinely performed to achieve bony union. The failure rate of spinal arthrodesis is significant because achieving adequate fixation of hardware in osteoporotic bone is difficult. Moreover, patients who are elderly have a reduced osteogenic potential. • Vertebroplasty and balloon kyphoplasty are indicated in patients with incapacitating and persistent severe focal back pain related to vertebral collapse.
  • 101. Dietary Measures • Adequate calcium and vitamin D intake are important in persons of any age, particularly in childhood as the bones are maturing, and are essential in the prevention and treatment of osteoporosis. • Vitamin D is increasingly being recognized as a key element in overall bone health, calcium absorption, balance (eg, reduction in risk of falls and muscle performance. • Patients who ingest inadequate amounts of vitamin D and calcium should receive oral supplementation.
  • 102. Physical and Occupational Therapy • Physical therapy - Physical therapy focuses on improving a patient's strength, flexibility, posture, and balance to prevent falls and maximize physical function. - Postural retraining is key in this population. Spinal bone mineral density (BMD) is directly correlated with the strength of the back extensors; therefore, maintaining and strengthening the back extensors should be emphasized.
  • 103. Occupational therapy • Training in the performance of activities of daily living (ADLs) and in the proper use of adaptive equipment are essential to the prevention of future falls. • Home modification focuses on reducing the risk of falling by installing handrails and grab bars in hallways, stairs, and bathrooms. • The use of a shower chair, tub bench, and adaptive bathing devices also can be beneficial. • The application of nonskid tape to steps (indoors and outdoors), as well as the removal of throw rugs, greatly improves home safety.
  • 104. Exercise • Aerobic low-impact exercises, such as walking and bicycling, generally are recommended. During these activities, ensure that the patient maintains an upright spinal alignment. • Proper therapy for osteoporosis includes 3-5 sessions per week of weight-bearing exercises, such as walking or jogging, with each session lasting 45-60 minutes. The patient should be instructed in a home-exercise program that incorporates the necessary elements for improving posture and overall physical fitness. • The physical therapist must address balance training, because fall prevention is important in eliminating the complication of fracture.
  • 105. Prevention of Osteoporosis • Primary prevention of osteoporosis starts in childhood. Patients require adequate calcium intake, vitamin D intake, and weight-bearing exercise. Beyond this, prevention of osteoporosis has two components: behavior modification and pharmacologic interventions. • The following behaviors should be modified to reduce the risk of developing osteoporosis: - Cigarette smoking - Physical inactivity - Intake of alcohol, caffeine, sodium, animal protein, and calcium
  • 106. Consultations • The most important consultation is with a rheumatologist or an endocrinologist. • These specialists can help obtain the proper laboratory tests and imaging studies needed to rule out causes of secondary osteoporosis. • In patients with uncontrolled pain that does not respond to conventional therapies, an invasive pain specialist may be consulted for proper interventional procedures
  • 107. • Consultation with a spine surgeon is appropriate for patients with intractable, severe, function-limiting symptomatology that has not been relieved by noninterventional techniques. • Consultation with a nonsurgical spine specialist is appropriate for a patient who is not a surgical candidate or whose symptoms persist despite surgical fixation
  • 108. Patient Education • Patient education is paramount in the treatment of osteoporosis. • Many patients are unaware of the serious consequences of osteoporosis, including increased morbidity and mortality, and only become concerned when osteoporosis manifests in the form of fracture; accordingly, it is important to educate them regarding these consequences. • Early prevention and treatment are essential in the appropriate management of osteoporosis.
  • 109. Thanks for Your Interest in preventing osteoporosis Email: dr.hishamdabbagh@gmail.com Email: haldabag@moh.gov.sa Mobile: 00966536715868