Osteoporosis in Postmenopausal Women

Background

• Osteoporosis in postmenopausal women is a common and undertreated systematic skeletal disorder, often leading to pain, morbidity, and increased mortality as a result of fragility fractures.
• Osteoporosis in postmenopausal women may be caused by aging and decreased gonadal function that is unassociated with another chronic illness (primary osteoporosis) or by chronic conditions or medications (secondary osteoporosis).
• Osteoporosis-related fractures (including hip and vertebral fractures) are the main complication of osteoporosis.

Evaluation

• Evaluate all postmenopausal women ≥ 50 years old for risk of osteoporosis (Weak recommendation).
• Obtain a detailed history and physical examination to assess risk factors for osteoporosis.
  • Ask about:
    • medical conditions and medications that increase the risk for osteoporosis
    • menstrual history
    • falls and/or fractures as an adult
    • a parental history of osteoporosis, hip fracture, or vertebral fracture
    • lifestyle factors that increase the risk for osteoporosis including excessive alcohol intake (> 3 drinks/day for women), tobacco use, low calcium or vitamin D intake, and low physical activity level
  • Assess skeletal deformities that may be a result of unrecognized fractures, such as:
    • height loss by comparing current height to maximum adult height
    • kyphosis
  • Assess localized vertebral spine tenderness, which may indicate an acute vertebral fracture.
  • Assess balance and mobility.
  • Determine overall frailty.
• Estimate the patient's probability of hip and any major osteoporosis-related fracture using a country-specific Fracture Risk Assessment (FRAX) (Weak recommendation).
• Evaluate for secondary causes of osteoporosis.
  • Consider performing blood tests, including:
    • 25-hydroxyvitamin D
    • serum total calcium
    • creatinine (with estimated glomerular filtration rate)
    • phosphorus
    • parathyroid hormone (PTH)
    • alkaline phosphatase
    • liver transaminases
    • complete blood count
  • Consider measuring the patient's 24-hour urinary calcium excretion, creatinine, and sodium to identify calcium malabsorption or hypercalciuria.
  • Consider additional studies in selected patients based on history or physical examination.
• Consider bone mineral density (BMD) testing based on the patient's clinical fracture risk profile and skeletal health assessment.
  • Use dual-energy x-ray absorptiometry (DXA) of the spine and hip when measuring BMD.
  • If BMD of the spine or hip is unable to be interpreted, then measure BMD at the 1/3 radius (lower arm) site.
• Evaluate for prevalent vertebral fractures during the initial exam (Strong recommendation) with either a vertebral fracture assessment (preferred) or lateral spine radiography. If a vertebral fracture assessment is unavailable or technically limited, then use lateral spine radiographs.
• Consider evaluation of bone turnover markers at the initial evaluation for osteoporosis if they would influence management decisions.
• Bone biopsy of the iliac crest with double tetracycline labeling is rarely used but may be helpful for patients with an unclear diagnosis to help differentiate renal osteodystrophy or osteomalacia from osteoporosis.
• Diagnosis of osteoporosis in postmenopausal women can include (depending on the organization's criteria):
  • the presence of a fragility fracture without other metabolic bone disorders, independent of BMD score (Weak recommendation)
  • a T-score ≤ -2.5 in the lumbar spine (anteroposterior), total hip, femoral neck, or 1/3 (33%) radius even without a prevalent fracture (Weak recommendation)
  • a T-score between -1 and -2.5 and high FRAX fracture probability using FRAX country-specific thresholds (Weak recommendation)

Management

• Management for all postmenopausal women with osteoporosis includes conservative management measures.
  • Address inadequate calcium intake and/or vitamin D deficiency (Strong recommendation).
  • Encourage patient to regularly engage in physical activity (including weight-bearing activities, resistance training, and balance exercises) (Strong recommendation).
  • Counsel on other lifestyle modifications, such as (Strong recommendation)
    • limiting alcohol intake to ≤ 2 drinks/day
    • smoking cessation if the patient is a current smoker or avoiding smoking if the patient is not a current smoker
  • Counsel women (particularly older women) on measures to reduce risk of falls (Strong recommendation), such as advising patient to perform core strengthening exercises.
• Administer pharmacologic therapy in postmenopausal women with (Strong recommendation):
  • a history of fragility fracture
  • a T-score of ≤ -2.5 in the spine, femoral neck, total hip or 1/3 (33%) radius
  • a T-score between -1 and -2.5 if the FRAX (or if available, trabecular bone score-adjusted FRAX) 10-year probability for a major osteoporosis fracture is ≥ 20% or 10-year probability of a hip fracture is ≥ 3% in the United States or above the country-specific threshold in other countries or regions

Table 1. Medication Dosing for Treatment of Osteoporosis in Postmenopausal Patients

• Goal of pharmacologic therapy is to prevent fractures. However, no medication can fully eliminate the risk of fracture.
• Select the type of pharmacologic therapy (either antiresorptive or anabolic) to treat postmenopausal women with osteoporosis based on patient-specific clinical factors (including risk of fractures), local guidelines, availability of medications, and patient preferences.
  • Antiresorptive medications include:
    • bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid)
    • denosumab
    • selective estrogen receptor modulators (raloxifene, bazedoxifene)
    • hormone replacement therapy (including tibolone)
  • Anabolic medications include:
    • parathyroid hormone (teriparatide) and parathyroid hormone-related protein analog (abaloparatide)
    • romosozumab
  • Administer alendronate, risedronate, zoledronic acid, or denosumab as the initial therapy for most postmenopausal women at a high risk of fracture (Strong recommendation).
  • If the patient is at a very high risk of fracture, treatment options include any of (Strong recommendation):
    • teriparatide
    • abaloparatide
    • romosozumab
    • zoledronic acid
    • denosumab
• After postmenopausal woman has completed course of romosozumab, teriparatide, or abaloparatide, treat patient with antiresorptive osteoporosis therapy (Strong recommendation).
• Consider alternative pharmacologic therapy for postmenopausal women who have recurrent fractures or significant bone loss while on therapy (Weak recommendation).
• Follow-up:
  • Annually reassess:
    • risk factors for falls and fractures
    • treatment compliance (for example, ask postmenopausal women treated with oral osteoporosis medications to describe the way they take their medication to ensure that the medication is being taken correctly as well as regularly)
    • calcium and vitamin D intake
    • medications that might contribute to bone loss
    • height
    • secondary causes of osteoporosis
  • Consider evaluating bone turnover markers at follow-up visits (Weak recommendation) if they would influence treatment decisions.
  • Bone mineral density testing:
    • Consider testing 1-2 years after starting medical therapy for osteoporosis (Weak recommendation).
    • Consider a longer interval between bone mineral density assessments depending on clinical circumstances (Weak recommendation).