This document summarizes osteoporosis, including its definition, diagnosis, risk factors, pathophysiology, and management. Osteoporosis is characterized by low bone mass and structural deterioration of bone, leading to an increased risk of fractures. It is diagnosed through bone mineral density tests such as DEXA scans. Risk factors include age, gender, family history, smoking, and medications. The condition results from imbalances in bone remodeling as one ages. Management involves lifestyle modifications and medications to reduce bone loss and promote formation, such as bisphosphonates, PTH analogues, and RANK ligand inhibitors.

1. Osteoporosis
BY : DR Jaskaran Singh Sandhu

2. • Osteoporosis as a clinical disorder is
characterized by an abnormally low bone mass
and defects in bone structure, a combination
which renders the bone unusually fragile and at
greater than normal risk of fracture in a person of
that age, sex and race.
• The cancellous regions are more porous and the
cortices thinner than normal

3. • World Health Organization’s definition
• Lumbar (L2-L4) density is 2.5 or more standard
deviations less than mean peak bone mass of
a healthy 25-year-old (T-score).
• Osteopenia: bone density is 1.0 to 2.5
standard deviations less than the mean peak
bone mass of a healthy 25-year-old

4. Regional osteoporosis
• osteoporosis is sometimes confined to a
particular bone or group of bones
(for example due to disuse, immobilization,
inflammation or pregnancy) – which
is usually reversible once the cause is
addressed.

5. Risk Factors For Osteoporosis
• Age
• Female
• Current use or frequent recent use of oral or
systemic glucocorticoids
• Family history of hip fracture
• Low body mass index (BMI) (less than
18.5 kg/m2)
• Smoking
• Alcohol intake of more than 14 units per week for
women and more than 21 units per week for men.

6. Secondary Causes of Osteoporosis
Endocrine
• Hypogonadism in either sex including untreated premature
menopause, treatment with aromatase inhibitors or androgen
deprivation therapy
• Hyperthyroidism
• Hyperparathyroidism
• Hyperprolactinaemia
• Diabetes
Respiratory
• Cystic fibrosis
• Smoking-related lung disease
Metabolic
• Homocystinuria
Chronic renal disease

7. Gastrointestinal
• Coeliac disease
• Inflammatory bowel disease
• Chronic liver disease
• Chronic pancreatitis
• Other causes of malabsorption
Rheumatological
• Rheumatoid arthritis
• Other inflammatory arthropathies
Haematological
• Multiple myeloma
• Haemoglobinopathies
Immobility
• Neurological injury
• Neurological disease

8. Clinical Features
• Most often patient
presents with
pathological fracture
due to trivial trauma
• Fracture of distal radius
(Colle’s)
• Vertebral fractures (MC)
• Hip fractures

9. Pathophysiology
• Peak bone mass
• Bone remodelling

10. Peak bone mass and Osteoporosis
• Peak bone mass is the maximum mass of bone
achieved by an individual at skeletal maturity,
typically between the ages of 25 and 35 years.
• After peak bone mass is obtained, both men and
women lose bone mass over the remainder of
their lifetimes
• Due to this subsequent bone loss, peak bone mass
is an important factor in the development of
osteoporosis.

12. Bone modelling and remodelling
• Modelling: During growth, the skeleton
increases in size by linear growth and by
apposition of new bone tissue on the outer
surfaces of the cortex
• Remodelling: It is a cellular process of bone
activity by which both cortical and cancellous
bone are maintained

13. • Osteoporosis results from a bone loss due to age
related changes in bone remodelling as well as
extrinsic and intrinsic factors that exaggerate this
process
• Bone remodelling has two main functions:
1. To repair micro damage within the skeleton to maintain
the skeletal strength
2. To supply calcium in order to maintain calcium levels
• Bone remodelling is also regulated by several
circulating hormones including:
– Estrogens
– Androgens
– Vitamin D
– Parathyroid hormone

14. RANK-RANKL receptor pathway for bone remodelling
• RANKL = receptor activated nuclear factor kappa ligand
• It is the cytokine responsible for communication
between the osteoblasts and other marrow cells and
osteoclasts
• It is secreted by the osteoblasts and certain cells of the
immune system
• The RANK receptor is present on the osteoclast
• The activation of RANK by RANKL is the final common
pathway for osteoclast differentiation and functioning
• Osteoprotegerin is a humoral decoy for RNAK secreted
by the osteoblasts

15. • Estrogens play an essential role in modulating the
secretion of osteoprotegerin (OPG) and RANKL
• In young adults, the resorbed bone is replaced by
an equal amount of new bone tissue  the mass of
the skeleton remains constant after peak bone
mass is achieved
• After age 30-45 years, the resorption and
formation processes become imbalanced 
resorption exceeds formation
• This imbalance may begin at different ages and
varies at different skeletal sites (exaggerated in
women after menopause)
• Excessive bone loss can be due to an increase in
osteoclastic activity and/or a decrease in
osteoblastic activity

16. Diagnosis
• Laboratory studies
– Complete blood count (CBC)
– Obtained to rule out secondary causes of low bone mass
• Vitamin D deficiency, hyperthyroidism, hyperparathyroidism,
hematologic disorders, malignancy ,Measurement of 24-hour urinary
calcium excretion
– Measurements of serum calcium, phosphorus, 25(OH)-vitamin D,
Alkaline phosphatase
– liver enzymes, creatinine
• Plain X-rays (bone loss > 30 %)

17. Bone Xray
• Apparent only after a 30% reduction in skeletal mass
• Even then one cannot tell whether this is due to osteoporosis
(a decrease in bone mass) or osteomalacia (insufficient
mineralization of bone) or a combination of both.
• Sometimes the term radiological osteopenia is used to
describe a mild or moderate loss of radiodensity in bone X-
rays without implying whether this is pathological.
• A more reliable sign is the presence of obvious fractures –
new and old – especially in the spine, ribs, pubic rami or
corticocancellous junctions of the long bones.

19. • Vertebral fracture can graded as
• Moderate and severe vertebral fracture predict
further hip fracture
Mild
• reduction
in height
• 20-25 %
Moderate
• 25-40%
Severe
• >40%

21. Singh’s Index

22. Special studies to evaluate bone mineral density
• Single-photon (appendicular) absorptiometry
• Double-photon (axial) absorptiometry
• Quantitative computed tomography (CT)
• Dual-energy x-ray absorptiometry (DEXA)
– Most accurate with less radiation
• Biopsy
– After tetracycline labeling
– To evaluate the severity of osteoporosis and identify osteomalacia
• Histologic changes:
– Thinning trabeculae
– Decreased osteon size
– Enlarged haversian and marrow spaces

23. DEXA( Dual energy Xray absorptiometry )
• Measure the amount of skeletal tissue by
evaluation of calcium content ( Bone mass)

25. Management
• Candidates for treatment are:
– Postmenopausal women
– Men aged 50 years and older
– With hip or vertebral fracture
– T score ≤ -2.5 at the femoral neck, total hip or lumbar
spine
– Low bone mass (T score between -1.0 and -2.5 at the
femoral neck or lumbar spine)
– A 10 year probability of a hip fracture ≥ 3 % or a 10
year probability of a major osteoporosis-related
fracture ≥ 20% (by FRAX score)

26. Non pharmacological –
prevention of osteoporosis
and osteoporotic fracture
• Nutrition
• Lifestyle modifications
• Prevention of fall
Basic therapeutic
measures
• Vitamin D and calcium
supplementation
• Estrogen and hormone
replacement therapy
(HRT)
Anti resorptive agents
• Calcitonin
• Bisphosphonates
• SERM
• Donesumab
Drugs stimulate
bone formation
• Sodium
Fluoride
• Exogenous PTH
• Vit D
analogues
Drugs with dual
action
• Strontium
Ranelate

27. Non pharmacologic
treatment
Dietary Changes
Balanced diet with
adequate calcium and
Vit D intake
Calcium rich sources:
milk, yogourt, ice
cream, cheese, cottage
cheese, almonds
Vit D sources:
Sunlight, fatty fish,
Lifestyle modifications
Weight bearing and
muscle strengthening
exercises
Cessation of smoking,
alcohol and high
caffeine intake
Adequate sun
exposure
Prevention of falls
Balance training and
lower limb
strengthening
exercises
Correction of sensory
impairment (vision and
hearing)

28. Pharmacologic treatment
1. Vitamin D supplementation
Recommended Daily Intake Age
200 IU < 50 years
400 IU 50-70 years
600 IU > 70 years
Treatment of Vit D deficiency:
60 000 IU 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
Maintenance therapy 1500-2000 IU/day

29. 2. Estrogens  reduce bone turnover, prevent bone loss, induce
small increases in bone mass of spine, hip and total body
Type of estrogen Dose
Esterified estrogen 0.3 mg/d
Conjugated equine estrogen 0.625 mg/d
Ethinyl estradiol 5 µg/d
Transdermal estrogen 50 µg/d
Many side effects are associated with use of estrogen:
- myocardical infarction
- stroke
- venous thromboembolic disease
- breast cancer
Therefore, estrogen/hormone therapy should not be used for
disease prevention (US preventive services task force)

30. 3. Selective Estrogen Receptor Modulator (SERMs)
Two SERMs are currently used in postmenopausal
women
i. Raloxifene 60 mg
ii. Tamoxifen 10 mg
iii. Bazedoxifene

31. Drug Advantages Side effects
Tamoxifen -Reduces bone turnover
and bone loss in
postmenopausal women
-Reduction in clinical
vertebral, hip and Colle’s
fracture
-increases the risk of
uterine cancer
- increases the risk of
venous thrombosis,
cataracts and possibly
stroke in postmenopausal
women
Raloxifene -Reduces bone turnover
and bone loss in
postmenopausal women
-Reduces the occurrence of
vertebral fracture by 30-
50%
-Reduction in invasive
breast cancer occurrence
- Increases the risk of deep
vein thrombosis and stroke
Bazedoxifene -prevent bone loss
- protects uterine tissue
from the effect of estrogen

32. 4. Bisphosphonates
- First line therapy
- Bisphosphonates are structurally related to
pyrophosphates, compounds that are incorporated into
the bone matrix
- They specifically impair the osteoclast function and
reduce the osteoclast number in part by apoptosis
- Also inhibit protein prenylation, one of the end products
in the mevalonic acid pathway, by inhibiting the enzyme
farnesyl pyrophosphate synthase
- This effect disrupts intracellular protein trafficking 
may lead to apoptosis

33. Alendronate
• Prevention: 35 mg weekly or 5 mg daily
• Treatment: 70 mg once weekly or 10 mg daily
(equivalence with regard to bone mass and bone
turnover responses)
• Given with full glass of water before breakfast due to its
poor absorption
• Side effects:
– Gastrointestinal side effects
– Esophageal irritation
• Patients are advised to remain upright for 30 minutes
after taking medication to avoid esophageal irriation

34. Etidronate
• Dose: 200 mg/day
• Not FDA approved for osteoporosis
• Efficacy against vertebral fracture when given
as intermittent cyclical regimen [2 weeks on,
2.5 months off]

35. Ibandronate
• 2.5 mg/day  Reduces vertebral fracture risk
by 40 %
• 150 mg/month PO or 3 mg every 3 months IV
 greater effect on turnover and bone mass
Risedronate
• Prevention and treatment 
– 5 mg daily tablet
– 35 mg weekly tablet
– 150 mg monthly tablet

36. Zoledronic acid
• Potent bisphosphonate highly effective in fracture
risk reduction
• 5 mg in 100 ml by slow IV infusion over 30 minutes
given annually
• Increased risk of transient post dose symptoms
(acute phase reaction)  fever, arthralgia,
myalgia, headache lasting for less than 48 hours 
to prevent give pre treatment acetaminophen
• Increased risk of atrial fibrillation
• Transient reduction in renal function

37. • Complications of bisphosphonates therapy
i. Gastrointestinal problems
ii. Osteonecrosis of jaw (long term use > 5
years)
iii. Low trauma atypical femur fractures (long
term use > 5 years)
iv. Contraindicated in patients with estimated
GFR below 30-35 ml/min

38. 5. Calcitonin
- Polypeptide hormone produced by thyroid gland
- Suppresses osteoclast activity by direct action on the
osteoclast calcitonin receptor
- Used for the treatment of osteoporosis in women who
are at least 5 years postmenopausal when alternate
treatments are not suitable
- Produces increments in bone mass of the lumbar spine
- Dose: 200 IU intranasal spray / 100 IU IM or SC daily
- Side effects:
- Rhinitis
- Epistaxis
- Allergic reactions

39. 6. Denosumab (RANKL inhibitor)
- Dose: 60 mg/6 months SC (arm, thigh, abdomen)
- FDA approved for treatment of postmenopausal
women with high risk of osteoporosis fractures +
those who have failed or are intolerant to other
therapies
- Monoclonal Ig2 agaisnt RANKL
- Reduces vertebral fractures (68%), hip fractures
(40%)
- Side effects:
- Arthralgia
- Nasopharyngitis
- Back pain
- C/I in severe hypocalcemia

40. 7. PTH, Teriparatide
- Endogenous PTH is an 84 amino acid peptide that is largely
responsible for calcium homeostasis
- Although chronic elevation of PTH (hyperparathyroidism)
is associated with bone loss, when given exogenously as a
daily injection it exerts anabolic effects on bone
- Approved for treatment of osteoporosis in both men and
women at high risk for fracture
- Receptors on osteoblasts (activates osteoblasts) and renal
tubule cells, also stimulates intestinal absorption of Ca and
PO4
- Dose: 20 µg daily SC injection (duration not to exceed 18-
24 months)
- Side effects: transient hypercalcemia, dizziness, nausea,
headache
- C/I in Paget’s disease (potential osteosarcoma risk)

41. 8. Strontium Ranelate
- 2 gm granules
- Increases bone mass throughout the skeleton
- Incorporated into hydroxyapatite, replacing
calcium  explains its fracture benefits
- Side effects:
- Increased risk of venous thrombosis
- Severe dermatologic reactions
- Seizures
- Abnormal cognition
- Increased risk of cardiovascular disease

42. THANK YOU