Osteoporosis is a progressive bone disease characterized by low bone mass and deterioration of bone tissue, leading to fragile bones that are prone to fractures. It is diagnosed based on bone mineral density measurements. Risk factors include older age, female sex, smoking, excessive alcohol use, low body weight, vitamin D and calcium deficiency, lack of exercise, and certain medical conditions or medications. Treatment focuses on lifestyle modifications to reduce risk factors as well as pharmacological therapies to prevent bone loss and reduce fracture risk. Common medications include bisphosphonates, calcitonin, estrogen therapy, SERMs, teriparatide, and denosumab.

1. OSTEOPOROSIS
Ajay Kumar Yadav
PGY3,Medicine
IOM-TUTH, Kathmandu

2. INTRODUCTION
• Osteoporosis is a progressive, systemic skeletal disorder characterised by low
bone mass and micro-architectural deterioration of bone tissue, with a
consequent increase in bone fragility and susceptibility to fracture.
• Osteoporosis = porous bone (greek derived)

3. DIAGNOSTIC CRITERIA

4. EPIDEMIOLOGY
• Bone formation > bone resorption in youth peak  peak bone mass in 25-30  Later, bone
resorption> bone formation.
• M=F ( F>M in postmenopausal d/t loss of bone protection from estrogen)
• In women, the loss of ovarian function at menopause (typically about age 50) precipitates rapid
bone loss so that most women meet the diagnostic criterion for osteoporosis by age 70–80.
• Above 50 years, the lifetime risk of a vertebral fracture is estimated to be one in three, and that
of hip fracture one in five.
• Common sites of fragility fracture include the vertebral bodies, distal radius, proximal humerus,
pelvis and proximal femur.

8. PATHOGENESIS
• Bone loss due to normal age related changes in bone remodelling as well as
extrinsic and intrinsic factors that exaggerate this process.
• Bone Remodelling has two primary functions:
• To repair micro damage within the skeleton to maintain skeletal strength.
• To supply calcium supply from the skeleton to maintain serum calcium.
• Excessive bone loss can be loss due to an increase in osteoclastic activity and/or
decrease in osteoblastic activity.

9. BONE REMODELLING

10. INTERACTION OF OSTEOBLAST Vs OSTEOCLAST : RANK
Receptor Vs RANL Ligand

12. RISK FACTORS

13. MODIFIABLE RISK FACTORS
• Smoking : BMD lower in smokers
• Alcohol : BMD lower in alcoholics
• Weight : Low BMI i.e. <19 is an indicator of low BMD
• Vitamin D and Calcium
• Exercise : Wt. bearing exercise increases BMD and prolonged bed rest decreases BMD

14. CAUSES

15. Cont..

16. APPROACH TO DIAGNOSIS

17. CLINICAL FEATURES
• Usually asymptomatic.
• Fractures of the spine( Dorso-lumbar spine being the most common), hip or wrist.
• Hip fractures are a/w a high incidence of DVT and PE(20–50%).
• Multiple vertebral fractures lead to height loss (often of several inches), kyphosis, and secondary
pain and discomfort related to altered biomechanics of the back.
• Thoracic fractures can be a/w restrictive lung disease.
• Lumbar fractures are associated with abdominal symptoms that include distention, early satiety,
and constipation

18. LAB EVALUATION

19. BIOCHEMICAL MARKERS OF BONE TURNOVER
BONE RESORPTION MARKERS BONE FORMATION MARKERS
Serum C-telopeptide (CTX) Serum bone-specific alkaline phosphatase
(BSAP), and
Urinary N-telopeptide (NTX) Osteocalcin (OC),
Amino terminal pro-peptide of type I procollagen
(PINP)

20. USES OF BIO-CHEMICAL MARKERS
• Predict risk of fracture independently of bone density in untreated pts
• Predict rapidity of bone loss in untreated pts
• 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 adequacy of pt compliance and persistence with osteoporosis therapy
• Help determine duration of “drug holiday” and when and if medication should be restarted

21. MEASUREMENT OF BONE MASS
• Dual-energy X-ray Absorptiometry(DXA) : Most preferred
• Single-energy X-ray Absorptiometry (SXA)
• Quantitative CT
• Ultrasound (US)

22. DEXA SCAN
• Femoral neck is the preferred site because of its higher PPV for fracture risk.
• Spine is not a suitable site for diagnosis in older people ; however, it is the
preferred site for assessing response to treatment.
• If hip measurement is not possible, spine BMD measurements may be used.
• If neither hip nor spine measurements are possible, BMD measurements at the
distal radius may be considered.

23. • Usually reported as T scores and Z scores
• Z score : Number of SD from the average bone mass of people of same age and
sex
• T score : Number of SD from the peak bone mass of young adults of the same sex
• T score between -1 and -2.5 : osteopenia
• T score -2.5 or less : osteoporosis
• T score -2.5 with a fracture : severe osteoporosis
• For every 1 decrease in T score, double risk of fracture.

24. Indications for BMD testing
• Women aged 65 and older and men aged 70 and older, regardless of clinical risk
factors.
• Younger postmenopausal women, women in the menopausal transition, and
men age 50 to 69 with clinical risk factors for fracture.
• Adults who have a fracture at or after age 50.
• Adults with a condition (e.g.) or taking a medication (e.g., glucocorticoids in a
daily dose ≥5 mg prednisone or equivalent for ≥3 months) a/w low bone mass or
bone loss

25. Indications for vertebral imaging
• All women age 70 and older and all men age 80 and older if BMD T-score 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)
• Prospective height loss of 0.8 in. or more (2 cm)
• Recent or ongoing long-term glucocorticoid treatment

26. FRACTURE RISK ASSESSMENT : FRAX TOOL

27. MANAGEMENT OF OSTEOPOROSIS

28. MANAGEMENT OF PATIENTS WITH FRACTURES
• Hip fractures almost always require surgical repair and include ORIF with pins
and plates, hemiarthroplasties, and total arthroplasties.
• Long bone fractures (e.g., wrist) often require either external or internal fixation.
• Fractures of vertebra, rib, and pelvis usually are managed with supportive care.

29. PAIN MANAGEMENT
• Acute pain management: Analgesics – NSAIDs and/or opioids.
• A few small, RCT suggest that calcitonin may reduce pain related to acute vertebral compression fracture.
• Percutaneous injection of artificial cement (polymethylmethacrylate) into the vertebral body
(vertebroplasty or kyphoplasty) may offer significant immediate pain relief in pts with severe pain from
acute or sub acute vertebral fractures.
• Cement leak : 10%
• Muscle spasms : muscle relaxants and heat treatments.
• Chronic pain: probably not bony in origin
• May require narcotic analgesics , frequent intermittent rest in a supine or semi-reclining position, heat
treatments, US and transcutaneous nerve stimulation

30. PSYCHOSOCIAL ASPECT OF OSTEOPOROSIS
• Address depression and falls secondary to disease.
• Family and social support is inevitable.

31. RISK FACTOR REDUCTION
• Adequate intake of calcium and vitamin D.
• Recommendations that men age 50–70 consume 1000 mg/day of calcium and that women age
51 and older and men age 71 and older consume 1200 mg/day of calcium.
• Vitamin D plays a major role in calcium absorption, bone health, muscle performance, balance,
and risk of falling.
• NOF recommends an intake of 800 to 1000 IU of vitamin D per day for adults age 50 and older.
• IOM Dietary Reference Intakes for vitamin D are 600 IU/ day until age 70 and 800 IU/day for
adults age 71 years and older.

35. Cont..
• Vitamin D deficiency 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.
• Maintenance therapy of 1500–2000 IU/day or whatever dose is needed to maintain the target blood
level.
• Regular weight-bearing and muscle-strengthening exercise.
• Fruits and vegetable containg Mg is essential for healthy bone.
• Patients should be educated to avoid consuming excessive amounts of Vit A as it have increased risk
of fracture in both men and women

36. • Abstinence from smoking and alcohol
• Smoking causes bone loss and increases hip fracture risk by several mechanisms:
• Early menopause
• Decrease BW
• Enhance estrogen metabolism
• Increase PTH conc.
• Decreased vitamin conc.
• Excessive alcohol use has been a/w low BMD and subsequent fracture and increased risk
of falls.
• Caffeine and Hypophosphatemia : Decreases the BMD.

37. PHARMACOLOGICAL THERAPY

38. PHARMACOTHERAPY Cont..
• Anti-resorptive agents : Bisphosphonates, SERMs, Calcitonin, Estrogen,
Denosumab, Phytoestrogen, Testosterone, Anabolic steroids
• Prevent bone loss and preserve architecture
• Improve quality of bone
• Reduce the risk of vertebral fractures (all agents)
• Alendronate, risedronate, zoledronic acid, and denosumab proved to reduce
the risk of nonvertebral and hip fractures
• Bone formation agents: Teriparatide, Strontium, Statins, Growth hormones and
factors, Fluoride
• Increases bone density and size
• Improves quality of bone
• Reduces the risk of vertebral and non vertebral fractures; no hip fracture data

39. BISHPHOSPHONATES
• MOA : Structurally related to pyrophosphates  incorporated into bone matrix
 specifically impair osteoclast function and reduce osteoclast number.
• INDICATIONS
• Postmenopausal osteoporosis
• Men with osteoporosis
• Glucocorticoid induced osteoporosis

40. Alendronate Ibandronate Sodium Risedronate Sodium Zoledronic acid
Dose 5 mg daily and 35
mg weekly tab for
prevention and
10 mg daily tablet,
70 mg weekly tablet
for treatment
150 mg monthly
tablet and 3 mg every
3 months by IV
injection.
5mg daily tab; 35 mg
weekly tab; 35 mg
weekly DR tab ;75
mg tab on two
consecutive days
every month; and
150 mg monthly tab
5 mg by IV infusion
over at least 15 min
once yearly for
treatment and once
every 2 years for
prevention
Fracture risk
reduction over 3
years
Spine and hip
fractures
By about 50 %
Vertebral fractures
By about 50 %
Vertebral fractures
by 41 to 49 % and
non-vertebral
fractures by 36 %
Vertebral fractures
by 70% , hip
fractures by 41 %,
and non vertebral
fractures by 25 % .

41. Cont..
• DRUG ADMINISTRATION
• Must be taken on an empty stomach, first thing in the morning, with plain water
• Must wait at least 30 min before eating, drinking, or taking any other medication.
• Pt. should remain upright (sitting or standing) during this interval (for Ibandronate at least 60 min)
• Delayed release tablets must be taken immediately after breakfast.
• SIDE EFFECTS
• GI : Esophagitis , Gastritis
• Osteonecrosis of the jaw (ONJ)
• Atypical femur fractures
• C/I:
• eGFR < 30–35 ml/min
• Hypocalcemia
• HSR
• Pregnancy and lactation
• Esophageal stricture or achalasia.

43. CALCITONIN
• FDA-approved for the t/t of osteoporosis in women who are at least 5 years
postmenopausal when alternative treatments are not suitable.
• Reduces vertebral fracture occurrence by about 30 % in those with prior vertebral
fractures.
• 200 IU delivered as a single daily intranasal spray
• S/E:
• Rhinitis,
• Epistaxis, and
• Allergic reactions(related to intranasal sprays)

44. ESTROGEN AND HORMONE THERAPY(ET/HT)
• FDA approved for the prevention of osteoporosis, relief of vasomotor symptoms, and
vulvo-vaginal atrophy associated with menopause.
• Reduces the risk of clinical vertebral fractures and hip fractures by 34 % and other
osteoporotic fractures by 23 %.
• Side effects: Increased risks of MI, stroke, invasive breast cancer, VT.
• Use of HRT for osteoporosis is generally restricted to younger postmenopausal women
who are at high risk of fracture and also have menopausal symptoms.
• When ET/HT treatments are stopped, bone loss can be rapid and alternative agents
should be considered to maintain BMD

45. SERMs
• RALOXIFENE
• FDA approved for both prevention and treatment of osteoporosis in postmenopausal women.
• Reduces the risk of vertebral fractures by about 30 % in pts with a prior vertebral fracture and by
about 55 % in pts without a prior vertebral fracture over 3 years.
• 60-mg tablet form daily to be taken with or without food.
• Side effects:
• Increases risk of DVT
• Hot flashes
• Leg cramps.

46. Cont..
• C/I:
• Women with child-bearing potential,
• Hx of venous thromboembolism or unexplained uterine bleeding.
• Hepatic impairment and
• Severe renal impairment
• Cautious use in women with a history of stroke or with risk of stroke.
• Indications :
• Alternative t/t option for the secondary prevention of osteoporotic fragility fractures in
postmenopausal women who have a contraindication to or intolerant of bisphosphonates.

47. TERIPERATIDE
• PTH analogue (1-34 aa)
• Indications
• Unable to tolerate or have C/I or unsatisfactory response for bisphosphonates.
• 65 years or older and have a T-score of –4.0 SD or below, or a T-score of –3.5 SD or below
plus more than two fractures, or who are aged 55–64 years and have a T-score of –4 SD or
below plus more than two fractures.
FDA approved for the treatment of
• Postmenopausal osteoporosis ,
• Men at high risk for fracture and
• Glucocorticoid therapy induced osteoporosis.
• When administered intermittently  anabolic skeletal effects, most marked in cancellous bone.

48. Cont..
• Reduces the risk of vertebral fractures by about 65 % and nonvertebral fragility fractures by about 53
% in pts. with osteoporosis, after an average of 18 months of therapy.
• 20 μg daily subcutaneous injection
• Treatment duration : not to exceed 18 to 24 months.
• Side effects:
• Leg cramps, nausea, and dizziness
• Increased risk of osteosarcoma (e.g., pts with Paget’s disease of bone and those having prior
radiation therapy of the skeleton),
• Bone metastases, hypercalcemia, or a Hx of skeletal malignancy should not receive teriparatide
therapy
• C/I: pregnancy, lactation, severe renal impairment

49. DENOSUMAB
• MOA: Human monoclonal antibody  Prevents RANKL from binding to its receptor, RANK 
Prevents differentiation of precursor cells into mature osteoclasts and decreases the function and
survival of activated osteoclasts.
• FDA approved for
• T/t of osteoporosis in postmenopausal women at high risk of fracture(2010),
• To treat bone loss in women with breast cancer on aromatase inhibitors,
• To treat bone loss in men receiving GNRH analogues for prostate cancer who are at high risk
for fracture(2011),
• Increase bone mass in men with osteoporosis at high risk for fracture(2012)
• Reduces the incidence of vertebral fractures by about 68 %, hip fractures, by about 40%, and
nonvertebral fractures by about 20% over 3 years
• Dose : 60 mg every 6 months as a subcutaneous injection.

50. Cont..
• Side effects:
• Hypocalcemia
• Increased the risk of serious skin infections (cellulitis) and skin rash
• ONJ
• Atypical femur fractures
• C/I: hypocalcemia, pregnancy, age ≤18 years

51. PHYTOESTROGENS
• The isoflavonoids (soy proteins) and lignans (flaxseed) are the most common
forms of phytoestrogens.
• Bone effects may be related to bone estrogen receptor agonist activity or
potentially direct or indirect effects on osteoblasts and osteoclasts.

52. TESTOSTERONE AND ANABOLIC STEROIDS
• In a few studies, women receiving methyl testosterone 1.25 or 2.5 mg oral daily
or testosterone implants 50 mg every 3 months had increased BMD.
• Testosterone, in various salt forms, was associated with increased BMD in some
studies when given to hypogonadal men and senior men with normal hormone
levels or mild hormonal deficiency.
• Transdermal gel, oral, intramuscular, and pellet testosterone products are
available

53. • HMG-COA REDUCTASE INHIBITORS (STATINS)
 Although observational studies have linked statin use with decreased fracture risk, a large case
control study did not demonstrate reduction in fracture risk for statin-treated patients
• FLUORIDE
 Unapproved therapy despite 30 years of clinical study
• GROWTH HORMONES AND FACTORS
 Recombinant IGF-1 injections, with or without IGF-3 binding protein, increased both bone
formation and resorption

54. SEQUENTIAL AND COMBINATION THERAPY
• For more severe osteoporosis, sequential treatment with anabolic therapy
followed by an antiresorptive agent is generally preferred
• Combination therapy with teriparatide and an antiresorptive can be considered
in pts with very severe osteoporosis such as spine and hip fractures.
• Combining two antiresorptive treatments is not recommended.

55. MONITORING OF PTS.
• Regular follow up
• Review their risk factors
• Encourage appropriate calcium and vitamin D intakes, exercise, fall prevention, and other
lifestyle measures.
• Continued review for need of medication
• Consideration of serial BMD testing(every 1 to 2 years is often appropriate), use of
biochemical markers, and vertebral imaging

56. POSTMENOPAUSAL OSTEOPOROSIS
• Alendronate or risedronate are first line treatments.
• If intolerant or contraindicated IV bisphosphonates or denosumab provide the most appropriate
alternatives.
• Raloxifene or HRT as additional options.
• High cost of teriparatide restricts its use to those at very high risk, particularly for vertebral
fractures.

57. OSTEOPOROSIS IN MEN
• Whom to treat ?
• Men who have had a hip or vertebral fracture without major trauma.
• Men who have not experienced a spine or hip fracture but whose BMD of the spine, femoral
neck, and/or total hip is 2.5 SD or below the mean of normal young white males.
• Men who have a T-score between 1.0 and 2.5 in the spine, femoral neck, or total hip plus a
10-yr risk of experiencing any fracture 20% or 10-yr risk of hip fracture 3% using FRAX;
• Men who are receiving long-term glucocorticoid therapy in pharmacological doses (e.g.
prednisone or equivalent 7.5 mg/d).
• Alendronate and risedronate are first line t/t.

58. • If contraindicated or intolerant zoledronic acid or denosumab provide the most appropriate
alternatives, with teriparatide as an additional option.
• For men at high risk of fracture who are receiving testosterone therapy, consider adding an agent
with proven antifracture efficacy (e.g. a bisphosphonate or teriparatide)
• Calcitonin, ibandronate, strontium ranelate should be used only if the approved agents for male
osteoporosis cannot be administered

59. GLUCOCORTICOID INDUCED OSTEOPOROSIS
• MOA :
 Inhibition of osteoblast function and an increase in osteoblast apoptosis.
 Stimulation of bone resorption, probably as a secondary effect.
 Impairment of the absorption of calcium across the intestine, probably by a vitamin D–independent effect.
 Increase of urinary calcium loss and perhaps induction of some degree of secondary hyperparathyroidism.
 Reduction of adrenal androgens and suppression of ovarian and testicular secretion of estrogens and
androgens.
 Induction of glucocorticoid myopathy, which may exacerbate effects on skeletal and calcium homeostasis as
well as increase the risk of falls.

60. • Bone loss and fracture risk increases with the dose and duration of therapy.
• T/t is recommended in men and women aged 18 years or over in whom therapy was
considered for 3 months or longer.
• Alendronate and risedronate are the first line options.
• If contraindicated or intolerant zoledronic acid, denosumab or teriparatide are
appropriate options.
• Adequate calcium and Vitamin D supplement.

61. THANK YOU