osteoporosis%20in%20women
OSTEOPOROSIS IN WOMEN
Osteoporosis is a progressive, systemic, skeletal disease characterized by decreased bone mass and microarchitectural deterioration of bone tissue leading to increased bone fragility and susceptibility to fractures.
The more risk factors (eg history of fracture, advanced age, comorbidities, etc) that are present, the greater the risk of fracture.

Pharmacotherapy

  • Choice of drug will depend not only on its capacity to increase bone mineral density (BMD) but also on reducing spine and hip fracture
  • Treatment is initiated in patients with or without a fragility fracture but with a T-score of ≤ -2.5; or in osteopenic patients without a fragility fracture but with a high fracture risk  
  • Therapy should be initiated without delay (2 weeks or more after a hip fracture) based on fracture risk in patients with recent fractures to prevent more fractures
    • Fracture within the past 2 years is a better predictor of imminent fracture risk (fracture within the next 2 years) than a distant fracture (>5 years ago)
  • Postmenopausal women 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 dual energy X-ray absorptiometry (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) and 10-year fracture risk assessment (FRAX) probability of >3% at the hip or >20% for major osteoporosis-related fracture in 10 years
  • If FRAX is not available, treatment may be initiated in patients >65 years with several risk factors and who are at high risk for osteoporosis
  • For GIOP, bone-protective therapy should be considered in patients ≥70 years old, on high-dose glucocorticoid therapy (≥7.5 mg/day), or with prior fragility fracture
    • On discontinuing glucocorticoids, treatment is continued similar to non-glucocorticoid osteoporosis for those with confirmed or high risk for osteoporosis
  • Duration of treatment is unknown, though several studies show treatment benefit when it is continued for 5 years
    • Longer courses may be beneficial for high-risk patients and after evaluating risks and benefits
  • Switching from antiresorptive therapy (bisphosphonates, Denosumab, HT, SERM, Strontium ranelate) to bone formation therapy (Teriparatide, Abaloparatide) is considered in the following women: 
    • With osteonecrosis of the jaw or atypical femoral fracture on antiresorptive therapy
    • With recurrent vertebral fractures due to osteoporosis
    • At high fracture risk and have been on long-term potent antiresorptive therapy and are sustaining fractures

Bisphosphonates

  • 1st-line of treatment for osteoporotic patients and patients receiving glucocorticoids with osteoporotic fractures or established osteoporosis
  • Inhibit osteoclast activity and decrease bone resorption
  • Have no effect on menopausal symptoms
  • Evaluate efficacy of treatment after 3 years on IV therapy and 5 years on oral therapy
    • If ineffective (ie declining BMD or recurrent low-trauma fracture), exclude secondary causes of osteoporosis and/or noncompliance
  • A bisphosphonate holiday may be given to patients on oral therapy after a stability of 5 years or on IV therapy after a stability of 3 years in low- to moderate-risk patients 
    • A bisphosphonate holiday is the temporary discontinuation of bisphosphonate therapy for up to 5 years or longer depending on the BMD and clinical circumstances of the patient; reassessment of fracture risk is done at 2- to 4-year intervals and osteoporosis therapy is re-initiated earlier than the 5-year suggested maximum if there is significant reduction in BMD or an intervening fracture
    • American Society for Bone and Mineral Research (ASBMR) Task Force on Long-Term Bisphosphonates has suggested a bisphosphonate holiday for low-moderate fracture risk and switching to another therapy or continuing bisphosphonate in those at high risk  
  • Bisphosphonate therapy is associated with possible risk of osteonecrosis of the jaw and atypical femur fracture 
  • Should not be given as initial therapy in patients with esophageal diseases, history of failed compliance with medication intake instructions and those with chronic renal disease

Alendronic acid

  • Used in the prevention and treatment of postmenopausal osteoporosis
    • Increases BMD, reduces risk of hip, spinal and non-vertebral fractures
  • Approved for the prevention (primary and secondary) and treatment of glucocorticoid-induced osteoporosis (GIOP)
    • Reduces risk of spinal fractures

Etidronic acid

  • Used in the prevention and treatment of postmenopausal osteoporosis
    • Increases BMD, reduces vertebral fractures
    • An observational study shows reduction in non-vertebral and hip fractures
  • Used in the prevention (primary and secondary) and treatment of GIOP
    • Reduces risk of spinal fractures

Ibandronic acid

  • Used in the prevention and treatment of postmenopausal osteoporosis
    • Increases BMD, reduces risk of vertebral fractures

Risedronic acid

  • Approved for the prevention and treatment of postmenopausal osteoporosis
    • Increases BMD, reduces risk of hip, spinal and non-vertebral fractures
  • Used in the prevention (primary and secondary) and treatment of GIOP
    • Reduces risk of spinal fractures

Zoledronic acid

  • Used in the prevention and treatment of postmenopausal osteoporosis
    • Increases BMD, reduces the risk of vertebral, non-vertebral and 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 and 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 and 6 yearly doses in high-risk patients  

Denosumab 

  • Approved for the treatment of osteoporosis in postmenopausal women at high risk of fracture  
    • Reduces the incidence of vertebral, hip, and non-vertebral fractures and improves BMD 
  • Also used for the treatment of bone loss in women with breast cancer on aromatase inhibitor treatment
  • Inhibits formation, function, and survival of osteoclasts leading to decreased bone resorption
  • Postmenopausal women with osteoporosis and are on Denosumab should be reassessed every 5-10 years for fracture risk
  • Administration should not be delayed or discontinued without subsequent antiresorptive therapy (eg bisphosphonates, HT, SERM) administered to prevent rebound in bone turnover and to decrease the risk of rapid BMD loss and risk of fracture
  • A drug holiday is not recommended to patients on Denosumab therapy

Parathyroid Hormone Therapy (PTH)

Teriparatide [Recombinant Human Parathyroid Hormone (1-34)]

  • Approved for the treatment of postmenopausal osteoporosis at high risk for fractures and with severe osteoporosis or osteoporosis not responsive to other anti-osteoporosis therapy
    • Increases BMD, reduces risk of spinal and non-vertebral fractures
  • Has been approved for use for a maximum of 24 months
  • May be used in the secondary prevention and treatment of GIOP
    • Increases BMD, reduces vertebral fractures
  • Stimulates new bone formation in cortical and trabecular bone
  • Has anabolic effects on bones
  • May follow treatment with a bisphosphonate or other antiresorptive agents to maintain or increase BMD

Abaloparatide

  • Newly approved human PTH-related peptide (PTHrP) analog indicated for the treatment of postmenopausal osteoporosis in women at high risk for fractures and in patients unresponsive or intolerant to other anti-osteoporosis therapy
  • Studies showed reduction in vertebral and non-vertebral fractures with long-term treatment 
  • Can also be used for up to 24 months and on completion of therapy, antiresorptive agents may be used to maintain BMD

Selective Estrogen Receptor Modulators (SERM)

Raloxifene

  • Considered treatment following poor tolerability with 1st-line agents
  • Approved for both prevention and treatment of postmenopausal osteoporosis
    • Increases BMD, reduces risk of vertebral fractures but not non-vertebral or hip fractures
  • May be a preferred treatment in women <65 years 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

Lasofoxifene

  • A 3rd-generation SERM newly approved for the prevention and treatment of postmenopausal osteoporosis 
  • Selectively binds to estrogen receptors thereby reducing the production and lifespan of osteoclasts, stimulation of osteoblast activity, with additional effects on calcium homeostasis
  • Studies showed reduction in vertebral and non-vertebral fractures with long-term treatment

Bazedoxifene

  • Approved as monotherapy in Germany, Japan, Israel and Sweden for prevention of osteoporosis in postmenopausal women at high risk of fracture and low risk of deep venous thrombosis, or with a high risk of breast cancer 

Hormonal Therapy

  • Primarily indicated for treatment of moderate-severe menopausal symptoms (eg vaginal atrophy, vasomotor symptoms) in healthy perimenopausal or menopausal women and for the prevention of osteoporosis
    • Increases BMD of lumbar spine and femoral neck, reduces risk of vertebral, non-vertebral and hip fractures
  • Physician and patient must consider risk vs benefit before using HT for the prevention of osteoporosis in women with menopausal symptoms; other treatments should be considered first 
  • When used for treatment of osteoporosis, hormone therapy should be administered in its lowest effective dose for the shortest duration due to possible risks (eg cerebrovascular accident, venous thromboembolism); abrupt treatment withdrawal is not recommended
    • Current data suggests that symptom recurrence is similar when hormone therapy is either tapered or abruptly discontinued
  • May be considered in women 50-59 years or postmenopause <10 years
  • Estrogen is used only in women with hysterectomy and not recommended for prevention of fractures in the absence of menopausal symptoms
  • For details on hormonal therapy in menopausal women, please see Menopause & Hormone Therapy Disease Management Chart

Activated Vitamin D

  • Used in the treatment of postmenopausal osteoporosis
    • Improves BMD and reduces vertebral fracture rate
  • Used in the prevention (primary and secondary) and treatment of GIOP
    • BMD improvement but no data to confirm reduction of vertebral fractures
  • Regulates the homeostasis of calcium (Ca) and bone formation
  • Limit concurrent use of Ca to <800 mg to decrease the risk of renal stone disease and hypercalcemia

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 in women who have been postmenopausal for >5 years and intolerant of bisphosphonates, hormone-based therapies, SERMs, Tibolone, Abaloparatide or Teriparatide, or when these treatment options are not appropriate
    • Increases BMD, reduces risk of spinal fractures
  • Inhibits osteoclast activity and decreases bone resorption
  • Has no effect on menopausal symptoms
  • Has analgesic effect for acute pain relief in osteoporotic fractures
  • May be considered for patients with GIOP if unable to tolerate oral or IV bisphosphonates or Teriparatide
  • Consider benefits of therapy versus risks including potential risk for malignancy with long-term use; limit use to <6 months

Strontium ranelate

  • Used for the treatment of severe osteoporosis in postmenopausal women for whom there are no other osteoporotic treatments due to contraindications or intolerance
    • Reduces the risk of vertebral and non-vertebral fractures
    • Reduces the risk of hip fractures in women ≥74 years of age with BMD T-score < -3
    • Prevents bone loss and vertebral fractures in osteopenic patients
  • Considered as an oral alternative for patients who have a contraindication to or are intolerant of oral bisphosphonate therapy
  • Stimulates the formation of new bone tissue and decreases bone resorption as proven in in vitro and experimental studies in animals and long-term clinical studies
  • Assessment of risk for cardiovascular disease development should be done prior to treatment and 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

Tibolone

  • A selective tissue estrogenic activity regulator (STEAR)
  • Approved for the prevention of postmenopausal osteoporosis
    • Data have demonstrated a reduction in vertebral fracture and improvement of BMD
  • Synthetic agent which has weak estrogenic, progestogenic and androgenic properties
  • Reduces menopausal symptoms but it does not stimulate uterine or breast tissues

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 and Teriparatide combination therapy than either agent alone, though there are no available fracture data  
  • SERM Bazedoxifene combined with conjugated estrogen may be considered for the prevention of postmenopausal osteoporosis when other osteoporosis therapies are not appropriate 
  • Added cost and potential increased side effects should be weighed against potential gains

Other Agents  

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 and fracture risk

Non-Pharmacological Therapy

Fall Prevention

  • Counsel the patient, especially the elderly, on ways to reduce risk of falls  
    • Measures to prevent falls (eg installing grab bars/handrails, nonslip flooring, adequate lighting, removing loose wires, keeping things within reach) 
    • Hip protectors may help reduce the impact on the hip during a fall  
  • Evaluate for certain medications (eg sedatives, hypnotics, narcotic analgesics, antihypertensives), neurologic conditions, alcohol, poor vision and hearing, frailty and deconditioning as these may lead to falls
  • Recommend exercise and physical therapy referral

Support Devices

  • Eg braces, lumbar corset, posture-training support devices
  • Recommended for patients with acute vertebral fractures or multiple vertebral fractures associated with chronic pain
  • Provides significant pain relief by decreasing the load on fracture sites and realigning the spinal column
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