This document summarizes osteoporosis, including its diagnosis, treatment, and management. It defines osteoporosis as a bone disease characterized by low bone mineral density (BMD). BMD testing is used to diagnose osteoporosis and assess fracture risk. Lifestyle modifications and medications can help prevent fractures by increasing BMD. Treatment options include antiresorptive drugs that decrease bone resorption, such as bisphosphonates, as well as anabolic drugs that stimulate new bone formation.

1. Osteoporosis
Diagnosis and Treatment

2. Osteoporosis is the most common bone disease in
humans, representing a major public health problem
as outlined in
Bone Health and Osteoporosis: A Report of the Surgeon
General (2004) [1].

3.  Osteoporosis is a silent disease until it is complicated by fractures—fractures that
occur following minimal trauma or in some cases, with no trauma.
 Fractures are common and place an enormous medical and personal burden on the
aging individuals who suffer them and take a major economic toll.
 Osteoporosis can be prevented, diagnosed, and treated before fractures occur.
 Even after the first fracture has occurred, there are effective treatments to decrease
the risk of further fractures.

4.  WHO diagnostic classification
Osteoporosis is defined by BMD at the hip or lumbar spine that
is less than or equal to 2.5 standard deviations below the mean
BMD of a young-adult reference population.

5. Diagnosis
 History
 Thorough clinical examination assessing risk factors and secondary causes of
osteoporosis

6. Lifestyle factors
Alcohol abuse, Excessive thinness
Excess vitamin A
High salt intake
Immobilization
Inadequate physical activity
Low calcium intake
Smoking (active or passive)
Vitamin D insufficiency
Genetic diseases
Cystic fibrosis
Ehlers-Danlos
Gaucher’s disease
Glycogen storage diseases Hemochromatosis
Homocystinuria
Hypophosphatasia
Marfan syndrome
Menkes steely hair syndrome
Osteogenesis imperfecta
Parental history of hip fracture
Porphyria
Riley-Day syndrome
Hypogonadal states
Androgen insensitivity
Anorexia nervosa Athletic amenorrhea
Hyperprolactinemia
Panhypopituitarism
Premature menopause (<40 years)
Turner’s and Klinefelter’s syndromes
Endocrine disorders
Central obesity
Cushing’s syndrome
Diabetes mellitus (types 1 and 2)
Hyperparathyroidism
Thyrotoxicosis

7. Gastrointestinal disorders
Celiac disease
Gastric bypass
Gastrointestinal surgery
Inflammatory bowel disease Malabsorption
Pancreatic disease
Primary biliary cirrhosis
Hematologic disorders
Hemophilia
Leukemia and lymphomas
Monoclonal gammopathies
Multiple myeloma
Sickle cell disease
Systemic mastocytosis
Thalassemia
Rheumatologic and
autoimmune diseases
Ankylosing spondylitis
Rheumatoid arthritis
Systemic lupus
Neurological and musculoskeletal risk
factors
Epilepsy
Multiple sclerosis
Muscular dystrophy
Parkinson’s disease
Spinal cord injury Stroke
Miscellaneous conditions and
diseases
AIDS/HIV
Amyloidosis
Chronic metabolic acidosis
Chronic obstructive lung disease
Congestive heart failure
Depression
End-stage renal disease
Hypercalciuria
Post-transplant bone disease
Sarcoidosis

8. Medications
Aluminum (in antacids)
Anticoagulants (heparin)
Anticonvulsants
Aromatase inhibitors
Barbiturates
Cancer chemotherapeutic drugs
Depo-medroxyprogesterone
Glucocorticoids
GnRH (gonadotropin-releasing hormone) agonists
Lithium
cyclosporine A and tacrolimus
Methotrexate
Total Parental nutrition
Proton pump inhibitors
Selective serotonin reuptake inhibitors
Tamoxifen
Thiazolidinediones

9.  The diagnosis of osteoporosis is established by measurement of BMD or by the
occurrence of adulthood hip or vertebral fracture in the absence of major trauma

10. Relationship Between Bone Density and
Bone Strength
 Bone density accounts for 60% to
80% of bone strength in untreated
patients
 Best early predictor of fracture risk
 Permits diagnosis before fractures
T-score
RelativeRisk
ofHipFracture
0
10
20
30
-5 -4 -3 -2 -1 0

11. Guidelines for Bone Density Testing
Screening
– All women age 65 and older
– All men age 70 and older
Test postmenopausal women and men >50 if:
– Fracture after age 50
– Clinical risk factors for osteoporosis
– Conditions/medications associated with bone loss

12. Ways of testing BMD
 Dual energy X-ray absorptiometry (DEXA)
 Peripheral dual energy X-ray absorptiometry (P-DEXA)
 Dual photon absorptiometry (DPA)
 Quantitative Computed Tomography (QCT)
 Quantitative Ultrasound

13. DEXA
 Most accurate and
standardized way of
measuring bone density
 Non invasive
 Uses two different low
dose X-ray beams to
estimate bone density in
spine and hip.

14. P-DEXA
 Portable
 Measure density in
peripheral sites
 Results – Quicker than
DEXA
 Disadvantage – Inability to
monitor treatment of
osteoporosis

15. Sites of measurement
 Apart from hip and spine peripheral parts where bone density is measured are
 Distal 1/3 Radius – Efficient in predicting fracture risk
 Proximal phalynx
 5th metatarsus
 Mid shaft tibia- Monitoring of osteoporosis treatment

16. Contraindications for BMD
 Pregnancy
 Recent gastrointestinal contrast studies. (recommended waiting for atleast 72 hrs)
 Body weight exceeding limit for DEXA >120-130 kgs
 Hip replacement or spinal instrumentation
 BMD measurement is not recommended in children or adolescents and is not
routinely indicated in healthy young men or premenopausal women unless there is
a significant fracture history or there are specific risk factors for bone loss.

17. Interpretation of Results
 Dexa measures BMD in grams of mineral per square centimeter of scanned bone
 Results are reported as
 T score (compared to a young-adult reference population of the same sex)
 Z score (compared to the BMD of an age-, sex-, and ethnicity-matched reference
population)
 The difference between the patient’s BMD and the mean BMD of the reference
population, divided by the standard deviation (SD) of the reference population, is
used to calculate T-scores and Z-scores.

19. FRAX
 FRAX® was developed by WHO to calculate
 10-year probability of a hip fracture and
 10-year probability of a major osteoporotic fracture (defined as clinical vertebral, hip,
forearm, or proximal humerus fracture)
taking into account femoral neck BMD and the clinical risk factors
 FRAX® algorithm is available at www.nof.org as well as at www.shef.ac.uk/FRAX,
also available on newer DXA machines.

23. Additional bone densitometry
technologies
 CT-based absorptiometry: Quantitative computed tomography (QCT)
measures volumetric integral, trabecular, and cortical bone density at the spine and
hip and can be used to determine bone strength, QCT and pQCT are associated
with greater amounts of radiation exposure than central DXA or pDXA.
 Trabecular Bone Score (TBS) is an FDA-approved technique which is available
on some densitometers. It may measure the microarchitectural structure of bone
tissue and may improve the ability to predict the risk of fracture.

24.  Quantitative ultrasound densitometry (QUS) does not measure
BMD directly but rather speed of sound (SOS) and/or broadband ultrasound
attenuation (BUA) at the heel, tibia, patella, and other peripheral skeletal sites.
 Validated heel QUS devices predict fractures in postmenopausal women
hip, and overall fracture risk) and in men 65 and older (hip and nonvertebral
fractures)

26. vertebral imaging
 All women age 70 and older and all men age 80 and older if BMD Tscore at the spine,
total hip, or femoral neck is ≤−1.0
 Women age 65 to 69 and men age 70 to 79 if BMD T-score at the spine, total hip, or
femoral neck is ≤−1.5
 Postmenopausal women and men age 50 and older with specific risk factors
 Low-trauma fracture during adulthood (age 50 and older)
 Historical height loss of 1.5 in. or more (4 cm)b
 Prospective height loss of 0.8 in. or more (2 cm)c
 Recent or ongoing long-term glucocorticoid treatment
 If bone density testing is not available, vertebral imaging may be considered based
on age alone
 Current height compared to peak height during young adulthood and Cumulative height loss measured
during interval medical assessment

27.  If bone density testing is not available, vertebral imaging may be considered based
on age alone
(Current height compared to peak height during young adulthood and Cumulative height loss
measured during interval medical assessment)
 Presence of a single vertebral fracture
increases the risk of subsequent fractures by 5-fold and the risk of hip and other
fractures 2-3 fold

28.  Vertebral imaging can be performed using
 lateral thoracic and lumbar spine X-ray or
 lateral vertebral fracture assessment (VFA), available on most modern DXA
machines.
 VFA can be conveniently performed at the time of BMD assessment, while
conventional X-ray may require referral to a standard X-ray facility.

29. Exclusion of secondary causes of osteoporosis
 Blood or serum
 Complete blood count (CBC)
 Chemistry levels (calcium, renal
function,
 phosphorus, and magnesium)
 Liver function tests
 Thyroid-stimulating hormone (TSH)
+/− free T4
 25(OH)D
 Parathyroid hormone (PTH)
 Total testosterone and gonadotropin in
younger men
 Bone turnover markers
 Consider in selected patients
 Serum protein electrophoresis (SPEP),
 serum immunofixation,
 serum-free light chains
 Tissue transglutaminase antibodies (IgA
and IgG)
 Iron and ferritin levels
 Homocysteine
 Prolactin
 Tryptase
 Urine
 24-h urinary calcium
 Consider in selected patients
 Protein electrophoresis (UPEP)
 Urinary free cortisol level
 Urinary histamine

30.  Biochemical markers of bone turnover may :
 Predict risk of fracture independently of bone density in untreated patients
 Predict rapidity of bone loss in untreated patients
 Predict extent of fracture risk reduction when repeated after 3–6 months of
treatment with FDA-approved therapies
 Predict magnitude of BMD increases with FDA-approved therapies
 Help determine duration of “drug holiday” and when and if medication should
be restarted

31. Osteoporosis management
 Universal recommendations for all patients
 Adequate intake of calcium and vitamin D
 lifelong participation in regular weight-bearing and muscle-strengthening exercise
 cessation of tobacco use
 identification and treatment of alcoholism
 Treatment of risk factors for falling

32. Benefits of exercise
Small (1% to 2%) effect on adult BMD
Reduces the loss of muscle mass
May reduce risk of falls by improving strength and balance
Regular walking decreases risk of hip fractures

33. Calcium Intake Recommendations

34. Vitamin D Intake Recommendations

35. Calcium supplements
Calcium salt Elemental calcium (%)
Carbonate 40
Tricalcium phosphate 38
Citrate 21
Lactate 13
Gluconate 9

36.  The body can absorb only about 500 milligrams of a calcium supplement at any
one time
 An extra 500-700mg of calcium per day is sufficient for most people to achieve
their appropriate daily calcium intake
 Carbonates – require gastric acidity
 Citrates – readily absorbable ( not dependent on acidic medium )

37. Interactions
 Decrease levels of the drug digoxin
 calcium and vitamin D supplements with digoxin or thiazides may also increase the
risk of hypercalcemia
 Also interact with fluoroquinolones, levothyroxine, antibiotics in the tetracycline
family, and phenytoin decreasing their absorption.
 Aluminum and magnesium antacids can both increase urinary calcium excretion
 Proton pump inhibitors decrease gastric acidity  decreased calcium absorption
 Mineral oil and stimulant laxatives can both decrease dietary calcium absorption

38. Calcium and bisphosphonates
 Bisphosphonate drugs are poorly absorbed from the GI tract and can bind calcium
 Therefore, bisphosphonate drugs should be taken on an empty stomach with a 30–
60 minute post-dose fast.
 To ensure adequate absorption, it is prudent to avoid taking calcium supplements
around the dose of oral bisphosphonates.

39.  Phytates (found in cereals, bran, soy beans, seeds) and oxalates (found in spinach,
rhubarb, walnuts), caffeine
 Inadequate vitamin D – Less calcium is absorbed in the intestines of people with
inadequate vitamin D levels.
 Long term treatments with steroids
 Kidney disease
 Side effects
 Nausea , vomitings , constipation, bloating, flatulence
 calcium supplements are associated with an increased risk of kidney stones in people
with a pre-existing high dietary calcium intake (≥1200mg/per day)

40. Vitamin D supplementation
 Most available supplements are Vit-D3 (cholecalciferol)
 D2 – Ergocalceferol is produced by UV light irradiating a plant compound
(ergostrol)
 A moderately fair person
 needs to expose their hands, face and arms (or equivalent area of skin
which is about 15% of the body surface) to sunlight
 for about 6-8 minutes
 4-6 times a week
 just before 10am or just after 3pm in summer
 Longer exposures would be needed in darker skinned individuals

41. GROUPS AT RISK OF VITAMIN D
DEFICIENCY ARE
 the elderly
 people who are house-bound or in residential care
 naturally dark-skinned people
 those who cover their skin for cultural or religious reasons
 babies of vitamin D deficient mothers.

42. Dietary sources of vitamin D
 fatty fish such as salmon, mackerel, and sardines which provide 300 to 600
units/3.5 ounces
 egg yolks which provide 20 units/yolk
 cod liver oil which provides 400 units/teaspoonful
 fortified foods such as milk, orange juice, and some cereals which provide about
100 units per serving

43.  Serum Vit D level between 20 and 40 (+/-10) ng/mL --
Normal
 An intake of 800 to 1000 international units (IU) of vitamin D3
per day for adults over age 50 is recommended.
 The safe upper limit for vitamin D intake for the general adult
population was set at 2,000 IU per day

44.  Adults who are vitamin D deficient may be treated with
 50,000 IU of vitamin D2 or vitamin D3 once a week
 or the equivalent daily dose (7000 IU vitamin D2 or vitamin D3) for 8–
12 weeks to achieve a 25(OH)D blood level of approximately 30 ng/ml
 Followed by maintenance therapy of 1500–2000 IU/day

46. Hypervitaminosis D
 fatigue
 loss of appetite
 weight loss
 excessive thirst
 excessive urination
 dehydration
 constipation
 irritability, nervousness
 ringing in the ear (tinnitus)
 muscle weakness
 nausea, vomiting
 dizziness
 confusion, disorientation
 high blood pressure
 heart arrhythmias

47. Long-term complications of untreated hypervitaminosis D
include:
kidney stones
kidney damage
kidney failure
excess bone loss
calcification (hardening) or arteries and soft tissues

48. Prevention Treatment
Approved Therapeutic Options
Estrogen
Alendronate
Risedronate
Ibandronate
Zoledronic acid
Raloxifene
Calcitonin
PTH (teriparatide)
Denosumab

49. Antiresorptive
Decrease bone resorption
Most treatment agents
Examples: Bisphosphonates, SERMs, calcitonin, estrogen,
denosumab
Anabolic
Stimulate bone formation
Example: Teriparatide

50. Bisphosphonates
 Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption
widely used in the management of osteoporosis and other diseases of high bone
turnover
 synthetic analogs of pyrophosphate, an endogenous regulator of bone
mineralization
 Two major classes
 Non-nitrogen containing class (e.g., clodronate, tiludronate and etidronate)
 Nitrogen-containing class (e.g., pamidronate, alendronate, ibandronate, riserdronate and
zoledronate)

51. Cellular Mechanism of Action
1. Osteoclast actively reabsorbs bone
matrix
2. BISPHOSPHONATE ( ) binds to bone
mineral surface
3. BISPHOSPHONATE is taken up by
the osteoclast
4. Osteoclast is inactivated
5. Osteoclast becomes apoptotic
(‘suicidal’) and dies
51

52. inhibiting
farnesyl
pyrophosp
hate
synthase
(FDPS)

53. Bisphosphonates
 Alendronate: 10 mg daily (tablet) or 70 mg weekly (tablet or liquid) for treatment, 5
mg daily or 35 mg weekly for prevention
 Risedronate: 5 mg daily or 35 mg weekly (tablet); 150 mg monthly (tablet)
 Ibandronate: 150 mg monthly by tablet; 3 mg intravenously over 15 to 30 seconds
every 3 months
 Zoledronic acid: 5 mg by intravenous infusion over a minimum of 15 minutes once
every year for treatment—and every other year for prevention

54. Indications
 Treatment and prevention of postmenopausal osteoporosis
 Alendronate, risedronate, ibandronate, zoledronic acid
 Prevention and/or treatment of glucocorticoid-induced
osteoporosis
 Risedronate, zoledronic acid, alendronate
 Treatment of men with low bone density
 Alendronate, risedronate, zoledronic acid

55.  Increased bone density in the spine by 5% to 8% and at the hip by 3% to 6% after 3
years
 Reduced incidence of vertebral fractures by 40% to 70%
 Alendronate, risedronate and zoledronic acid reduced non-vertebral fractures (25%
to 40%), including hip fractures (40% to 60%), in women with osteoporosis
 Ibandronate: Overall, no effect observed on non-vertebral or hip fractures. In a
post-hoc analysis, non-vertebral fracture reduction was seen in a high-risk
subgroup with a baseline femoral neck T-score less than -3.0

56. Contraindications/Warnings/Precautions
 Hypocalcemia
 Creatinine clearance <30 cc/min (<35 cc/min for zoledronic acid)
 For oral dosing: Esophageal stricture or impaired esophageal motility
(alendronate); inability to stand or sit for at least 30 minutes
(alendronate/risedronate) or 60 minutes (ibandronate)

57.  Oral dosing requirements
 Tablets (with exception of delayed release risedronate) taken on an empty stomach
overnight fast with 6 to 8 oz of plain water while in an upright position
 Patients should not eat or lie down for at least 30 minutes (alendronate
and risedronate) or 60 minutes (ibandronate)
 Calcium and vitamin D supplements, if needed, should be taken at a different time of
than the oral bisphosphonate

58. Side effects
 gastrointestinal problems such as difficulty swallowing and inflammation of the
esophagus and stomach.
 Osteonecrosis of the Jaw
 Atypical Fractures of Femur

59. Bisphosphonate holiday
 In patients at high risk for fractures, continued treatment seems reasonable.
Consider a drug holiday of 1 to 2 years after 10 years of treatment
 For lower risk patients, consider a “drug holiday” after 4 to 5 years of stability
 Follow BMD and bone turnover markers during a drug holiday period, and
reinitiate therapy if bone density declines or markers increase

60. Hormone replacement therapy
 HRT has been shown to significantly decrease the number of fractures at hip and
spine
Skeletal effects:
Decrease in biochemical markers of 50% to 60%
2-year BMD increase of 4% to 6% at hip and spine
Decreased incidence of vertebral and hip fractures (34%) after 5 years

61. Adverse effects of HRT
 Breast cancer
 Venous thromboembolism
 Stroke
 Ovarian cancer
 Endometrial cancer
 Coronary heart disease
 Dementia

62. HRT
 HRT is available in a wide variety of oral as well as transdermal preparations
including estrogen only, progestin only and combination estrogen–progestin.
 HRT dosages include cyclic, sequential, and continuous regimens.
Recommendations:
 HRT should be considered for women younger than 60 in which the benefits outweigh
the risks especially for those who cannot tolerate other osteoporosis treatments
 Recommended as a treatment option for osteoporosis in women who have undergone
an early menopause
 For all women, the lowest effective dose should be used for the shortest time

63. The Concept of a SERM
Selective Estrogen Receptor Modulator
(EAAs: Estrogen Agonist/Antagonists)
 Binds to the estrogen receptors
 Produces an estrogen agonist effect in some
tissues (bone, serum lipids, and arterial
vasculature)
 Produces an estrogen antagonist effect in
others ( breast and uterus )

64. Raloxifene
• Raloxifene (60 mg daily)
• Skeletal effects:
 Decrease in biochemical markers of 30%
 3-year BMD increases of 2% to 3% at hip and spine
 Decreased incidence of vertebral fractures (30% to 50%) in
women with pre-existing vertebral fractures or low bone density.
No effect on non vertebral or hip fractures has been observed
• Extra-skeletal effects: reduction in invasive
breast cancer

65. Raloxifene
Adverse effects
 Hot flashes
 2- to 3-fold increased risk of venous
thromboembolic events
 No increased risk of stroke, but increased risk
of death following stroke
 Leg cramps

66. Denosumab
 Monoclonal antibody to RANKL
 60 mg subcutaneous injection every 6 months
 9% increase in spinal BMD after 3 years in the pivotal
FREEDOM trial; 4% to 5% increase in hip BMD
 Reduction in fracture risk after 3 years:
 68% decrease in new vertebral fractures
 40% decrease in hip fractures
 20% decrease in nonvertebral fractures
 8-year data: continued increase BMD, reduced bone
turnover, good safety

67. Denosumab Adverse Events
 Serious infections leading to hospitalization
 Dermatitis, eczema, rashes
 Back pain, pain in the extremity, musculoskeletal
pain, hypercholesterolemia, cystitis
 Pancreatitis
 Osteonecrosis of the jaw
 Significant suppression of bone remodeling

68. Calcitonin
 Calcitonin (200 units daily by nasal spray)
 Skeletal effects:
 Decrease in biochemical markers of 20%
 Small effect (1% to 2%) on bone density in spine
 Reduced incidence of vertebral fractures (36%) in women with pre-
existing vertebral fractures
 No effect on nonvertebral or hip fractures has been observed
 Adverse effects
 Nasal stuffiness, rhinitis, epistaxis
 Possible increased cancer risk

69. Calcitonin
 Approved for the treatment of osteoporosis in women who are at least 5 years
postmenopausal when alternative treatments are not suitable

70. Teriparatide: rhPTH [1-34]
 The only treatment agent that is anabolic—stimulates
bone
formation rather than inhibiting bone resorption
 20 μg daily (subcutaneously) for no more than 2 years
 Indication: treatment of men and postmenopausal women
with osteoporosis who are at high risk for fracture

71. Effects:
Increased bone density in spine by 9% and hip by
3% vs placebo over 18 months
Reduced incidence of vertebral fractures (65%) and
nonvertebral fragility fractures (53%) in women with
pre-existing vertebral fractures
Studies too small to evaluate effect on hip fractures
Adverse reactions:
 arthralgia
 pain
 Nausea
 osteosarcoma risk in rats

72. Sequential and combination therapy
 For more severe osteoporosis, sequential treatment with
anabolic therapy followed by an antiresorptive agent is
generally preferred to concomitant combination therapy.
 few indications for combining two antiresorptive treatments,
considered in the short term in women who are experiencing
 active bone loss while on low dose HT for menopausal symptoms
 or raloxifene for breast cancer prevention.

73. Duration of treatment
 No pharmacologic therapy should be considered indefinite in duration
 All nonbisphosphonate medications produce temporary effects that wane upon
discontinuation
 Bisphosphonates may allow residual effects even after treatment discontinuation
 Evidence of efficacy beyond 5 years is limited

74. Monitoring treatment
 encourage continued and appropriate compliance with their osteoporosis
therapies
 review their risk factors and encourage appropriate calcium and vitamin D
intakes, exercise, fall prevention, and other lifestyle measures
 Accurate yearly height measurement is a critical determination of
osteoporosis treatment efficacy
 Loss of 2 cm (or 0.8 in.) or more in height either acutely or cumulatively 
repeat vertebral imaging test to determine if new or additional vertebral
fractures have occurred

75. Physical medicine and rehabilitation
 reduce disability
 improve physical function
 lower the risk of subsequent falls
 Recommendations
 improve posture and balance and strengthen quadriceps muscles to allow a person to
rise unassisted from chair
 prescription for assistive device for improved balance with mobility
 complete exercise recommendation that includes weightbearing aerobic activities for the
skeleton, postural training, progressive resistance training for muscle and bone
strengthening

76.  Advise patients to avoid forward bending and exercising with trunk in flexion,
especially in combination with twisting.

77. Thank you