osteoporosis
OSTEOPOROSIS
Osteoporosis is the progressive, systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility and susceptibility to fractures.
The more risk factors (eg history, of fracture, advanced age, comorbidities, impaired vision) that are present, the greater the risk of fracture.

Principles of Therapy

  • Choice of drug will depend not only on its capacity to increase BMD but also on reducing spine & hip fracture
  • Postmenopausal women & men ≥50 years old with the following should be considered for treatment:
    • Low-trauma hip, vertebral or wrist fracture
    • T-score of ≤ -2.5 at the femoral neck, total hip, lumbar spine, or 33% radius by DXA
    • Low bone mass (T-score between -1.0 and -2.5 at the femoral neck, lumbar spine, total hip, or 33% radius by DXA, osteopenia) & 10-year FRAX™ fracture probability of ≥3% at the hip or >20% for major osteoporosis-related fracture at 10 years
  • If FRAX™ is not available, treatment may be initiated in patients >65 years old with several risk factors & who are at high risk of osteoporosis
  • On discontinuing glucocorticoids, treatment in continued similar to non-glucocorticoid osteoporosis for those with confirmed or high risk for osteoporosis

Pharmacotherapy

Bisphosphonates
  • 1st-line of treatment for osteoporotic patients & patients receiving glucocorticoids with osteoporotic fractures or established osteoporosis
  • Inhibits osteoclast activity & potent inhibitors of bone resorption
  • Have no effect on menopausal symptoms
  • Evaluate efficacy of treatment after 3 years on IV therapy & 5 years on oral therapy
    • If ineffective (ie declining BMD or recurrent low-trauma fracture), exclude secondary causes of osteoporosis &/or noncompliance
  • A bisphosphonate holiday may be given to patients on oral therapy after a stability of 5 years in moderate-risk patients or of 6-10 years in high-risk patients
  • Bisphosphonate therapy is associated with possible risk of osteonecrosis of the jaw & atypical femur fracture
Alendronic acid
  • Used in the prevention & treatment of postmenopausal osteoporosis
    • Increases bone mineral density (BMD), reduces risk of hip, spinal & non-vertebral fractures
  • Approved for the treatment of osteoporosis in men
    • Increases bone mineral density (BMD), reduces risk of spinal fractures
  • Approved for the prevention (primary & secondary) & treatment of glucocorticoid-induced osteoporosis (GIOP) in men & women
    • Reduces risk of spinal fractures
Etidronic acid
  • Used in the prevention & treatment of postmenopausal osteoporosis
    • Increases bone mineral density (BMD), reduces vertebral fractures
    • An observational study shows reduction in non-vertebral & hip fractures
  • Used in the prevention (primary & secondary) & treatment of glucocorticoid-induced osteoporosis (GIOP)
    • Reduces risk of spinal fractures
Ibandronic acid
  • Used in the prevention & treatment of postmenopausal osteoporosis
    • Increases bone mineral density (BMD), reduces risk of vertebral fractures 
Risedronic acid
  • Approved for the prevention & treatment of postmenopausal osteoporosis in women
    • Increases bone mineral density (BMD), reduces risk of hip, spinal & non-vertebral fractures
  • May be used in the treatment of osteoporosis in men
    • Increases bone mineral density (BMD)
    • Reduces the risk of hip fractures in men with stroke & concomitant osteoporosis
    • Reduces the risk of spinal fractures in men with idiopathic osteoporosis
  • Used in the prevention (primary & secondary) & treatment of glucocorticoid-induced osteoporosis (GIOP) in men & women
    • Reduces risk of spinal fractures
Zoledronic acid
  • Used in the prevention & treatment of postmenopausal osteoporosis
    • Increases bone mineral density (BMD), reduces the risk of vertebral, non-vertebral & hip fractures
  • Also indicated in the prevention of new clinical fractures in patients who recently had a low-trauma hip fracture
  • Also recommended in the prevention & treatment of osteoporosis in women expected to be on glucocorticoid treatment for at least 12 months
  • A drug holiday may be given to patients on IV therapy following 3 yearly doses in moderate-risk patients & 6 yearly doses in high-risk patients
Hormonal Therapy1(HT)
  • Primarily indicated for treatment of moderate-severe menopausal symptoms (eg vaginal atrophy, vasomotor symptoms) in healthy perimenopausal or menopausal women & for the prevention of osteoporosis
    • Increases bone mineral density (BMD) of lumbar spine & femoral neck, reduces risk of vertebral, non-vertebral & hip fractures
    • Physician & patient must consider risk versus benefit before using hormonal therapy (HT) as 1st-line treatment for the prevention of osteoporosis in women with menopausal symptoms; other treatments should be considered first
  • When used for treatment of osteoporosis, hormonal therapy (HT) should be administered in its lowest effective dose for the shortest duration due to possible risks; abrupt treatment withdrawal is not recommended
    • Current data suggests that symptom recurrence is similar when hormonal therapy is either tapered or abruptly discontinued
  • May be considered in women 50-59 years of age or postmenopause <10 years
  • Estrogen is not recommended for prevention of fractures in the absence of menopausal symptoms

1For details on hormonal therapy in menopausal women, please see Menopause & Hormone Therapy Management Chart. 

Parathyroid Hormone
Teriparatide [Recombinant human Parathyroid Hormone (PTH) (1-34)]
  • Approved for the treatment of postmenopausal osteoporosis & for men at high risk for fractures & with severe osteoporosis or osteoporosis not responsive to other anti-osteoporosis therapy
    • Increases bone mineral density (BMD), reduces risk of spinal & non-vertebral fractures
  • Has been approved for use for a maximum of 24 months
  • Indicated to increase bone mineral density (BMD) in men with primary or hypogonadal osteoporosis at risk of fracture
  • May be used in the prevention & treatment of glucocorticoid-induced osteoporosis (GIOP)
    • Increases bone mineral density (BMD), reduces vertebral fractures
  • Stimulates new bone formation in cortical & trabecular bone
  • Has anabolic effects on bones
  • May follow treatment with a bisphosphonate or other antiresorptive agents to maintain or increase bone mineral density (BMD)
Receptor Activator of Nuclear Factor Kappa-B (RANK) Ligand (RANKL)/ RANKL Inhibitor
Denosumab
  • Approved for the treatment of osteoporosis in men & postmenopausal women at high risk of fracture
    • Reduces the incidence of vertebral, hip, & non-vertebral fractures & improves bone mineral density (BMD)
  • Also used for the treatment of bone loss in women with breast cancer on aromatase inhibitor treatment, bone loss in men receiving prostate cancer treatments who are at high risk for fracture, & for increasing bone mass in men at high risk of fracture
  • Inhibits formation, function & survival of osteoclasts leading to a decreased bone resorption
  • A drug holiday is not recommended to patients on Denosumab therapy
Selective Estrogen Receptor Modulator (SERM)]
Raloxifene
  • Considered as treatment following poor tolerability with 1st-line agents
  • Approved for both prevention & treatment of postmenopausal osteoporosis
    • Increases bone mineral density (BMD), reduces risk of vertebral fractures but not non-vertebral fractures
  • May be preferred treatment in women <65 years old without a hip fracture history
  • Binds to estrogen receptors in target organs to produce various estrogenic effects
  • Reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis
Strontium ranelate
  • Used for treatment of severe osteoporosis in postmenopausal women for whom there are no other osteoporotic treatments due to eg contraindications or intolerance
    • Reduces the risk of vertebral & non-vertebral fractures
    • Reduces the risk of hip fractures in women ≥74 years of age with bone mineral density (BMD) T-score < -3
    • Prevents bone loss & vertebral fractures in women with osteopenia
  • Considered as an oral alternative for patients with contraindications to or are intolerant of oral bisphosphonate therapy
  • Stimulates the formation of new bone tissue & decreases bone resorption as proven in in vitro & experimental studies in animals & long-term clinical studies
  • Assessment of risk for cardiovascular disease development should be done prior to treatment & should be monitored every 6-12 months
    • Treatment should be stopped if patient develops cerebrovascular disease, ischemic heart disease, uncontrolled hypertension or peripheral arterial disease
Calcitonin
  • 32 amino acid hormone secreted by C cells of the thyroid gland
  • Usually considered 2nd-line treatment in patients unwilling or unable to take other osteoporotic agents
  • Approved for the treatment of osteoporosis
    • Increases bone mineral density (BMD), reduces risk of spinal fractures
  • In glucocorticoid-induced osteoporosis (GIOP), is considered only for patients unable to tolerate oral or IV bisphosphonates or Teriparatide
  • Inhibits osteoclast activity & decreases bone resorption
  • Has no effect on menopausal symptoms
  • Has analgesic effect for acute pain relief in osteoporotic fractures
  • Consider benefits of therapy versus risks including potential risk for malignancy with long-term use; limit use to <6 months
Activated Vitamin D
  • Used in the treatment of postmenopausal osteoporosis
    • Improves bone mineral density (BMD) & reduces vertebral fracture rate
  • Used in the prevention (primary & secondary) & treatment of glucocorticoid-induced osteoporosis (GIOP)
    • Bone mineral density (BMD) improvement but no data to confirm reduction of vertebral fractures
  • Regulates the homeostasis of calcium & bone formation
  • Limit concurrent use of calcium to <800 mg to decrease the risk of renal stone disease & hypercalcemia
Tibolone
  • A selective tissue estrogenic activity regulator (STEAR)
  • Approved for the prevention of postmenopausal osteoporosis
    • Data have demonstrated a reduction in vertebral fracture & improvement of bone mineral density (BMD)
  • Synthetic agent which has weak estrogenic, progestogenic & androgenic properties
  • Reduces menopausal symptoms but it does not stimulate uterine or breast tissues
Testosterone
  • Suggested in men at borderline high risk for fracture who have serum testosterone levels <200 ng/dL that is accompanied by signs or symptoms of androgen deficiency or organic hypogonadism
  • Also suggested in men at high risk for fracture with testosterone levels <200 ng/dL who lacks standard indications for testosterone therapy but who have contraindications to approved pharmacological agents for osteoporosis
  • Many studies have demonstrated that replacement therapy increases bone mineral density (BMD) in men with hypogonadism, however, effects on fracture reduction are unclear
Combination Therapy
  • Combination of a bisphosphonate with  a non-bisphosphonate can provide additional small increase in BMD when compared with monotherapy
  • A better BMD response is seen with Denosumab & Teriparatide combination therapy than either agent alone, though there are no available fracture data
  • Added cost & potential increased side effects should be weighed against potential gains
Other Agents
Combination Bazedoxifene & Conjugated Estrogen
  • SERM Bazedoxifene combined with Estrogen may be considered for the prevention of postmenopausal osteoporosis
Sodium fluoride (Na fluoride)
  • Stimulates bone formation
  • Further studies are needed to prove the efficacy of Sodium fluoride in reducing fracture risk
Genistein
  • A tyrosine kinase inhibitor used in the management of menopausal symptoms
  • Further studies are needed to prove its benefit on bone health & fracture risk

Non-Pharmacological Therapy

Nutrition
Calcium (Ca) & Vitamin D
  • Prevention of osteoporosis
    • Lifelong intake of adequate calcium (Ca) is associated w/ higher peak bone mass which reduces the risk of osteoporosis/fracture in later life
    • Recommended calcium (Ca) intake: 1000 mg/day for men 50-70 years old; 1200 mg for women ≥51 years old & men ≥71 years old
    • The main sources of calcium (Ca) are dairy products; vegetables (eg broccoli, cabbage) are also a good source
    • Vitamin D helps in intestinal calcium (Ca) absorption, bone mineralization, & enhance response to bisphosphonate therapy
    • Recommended Vitamin D intake for patients >50 years of age: 800-1000 IU/day
      • Higher doses may be needed in patients with malabsorption, obesity, older individuals, transplant patients
    • 25 (OH) D blood levels of >20 ng/ml is a good index for adequate bone health & Vitamin D stores
    • The main sources of Vitamin D are from sun exposure (>15 minutes/day), fortified milk, cereals, egg yolks, salt water fish & liver
  • Treatment of osteoporosis
    • Calcium & Vitamin D supplements may be administered as adjunct to other drug therapies in the treatment of osteoporosis
    • Help to increase bone mineral density (BMD) & may reduce fracture risk in men & postmenopausal women with osteoporosis
  • Glucocorticoid-Induced Osteoporosis
    • Recommended for prevention & treatment
    • Has been shown to reduce bone loss
Good General Nutrition
  • Excessive dieting & low body weight is associated with increased risk of fracture
    • Recommend BMI ≥19 kg/m2
  • Maintenance of adequate energy & protein intake (US RDA 0.8 g/kg) is important as well as consuming a balanced diet
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