SHARE

Key Points

  • Treat high risk individuals - particularly those with previous fracture.
  • Consider bisphosphonates as the first line therapeutic choice for postmenopausal women at high risk of fracture.
  • Reassess fracture risk after patient has been on bisphosphonates for 3-5 years.
  • Following reassessment, prescribe a “bisphosphonate holiday” for women who are on bisphosphonates and are low-to-moderate risk of fracture.
  • Consider anabolic therapy (teriparatide or abaloparatide) for women at very high risk of fractures, including those with multiple fractures.
  • All women undergoing treatment with osteoporosis therapies other than anabolic therapy should consume calcium and vitamin D in their diet or via supplements.
  • Monitor the BMD of high-risk individuals with a low BMD every 1 to 3 years.

Treatment and Management

Who to Treat

  • 1.1 Endocrine Society (ES) recommends treating postmenopausal women at high risk of fractures, especially those who have experienced a recent fracture, with pharmacological therapies, as the benefits outweigh the risks. (1|⊕⊕⊕⊕)

Bisphosphonates

  • 2.1 In postmenopausal women at high risk of fractures, ES recommends initial treatment with bisphosphonates (alendronate, risedronate, zoledronic acid, and ibandronate) to reduce fracture risk. (1|⊕⊕⊕⊕)

    Technical Remark:

    • Ibandronate is not recommended to reduce nonvertebral or hip fracture risk.
  • 2.2 In postmenopausal women with osteoporosis who are taking bisphosphonates, ES recommends that fracture risk be reassessed after 3-5 years, and women who remain at high risk of fractures should continue therapy, while those who are at low-to-moderate risk of fractures should be considered for a “bisphosphonate holiday.” (1|⊕⊕◯◯)

    Technical Remarks:

    • A bisphosphonate holiday is operationally defined as a temporary discontinuation of bisphosphonate for up to 5 years. This period may be longer depending on the BMD and clinical circumstances of the individual patient.
    • The evidence is stronger for retention of benefits during a holiday for alendronate and zoledronic acid where there are randomized extension trials.
    • A shorter reassessment period of 3 years is more appropriate for annual intravenous zoledronic acid (5 mg) based on evidence from RCTs showing residual effects after 3 years of annual use.
    • Once a bisphosphonate holiday is initiated, reassess fracture risk at 2- to 4-year intervals and consider reinitiating osteoporosis therapy earlier than the 5-year suggested maximum if there is a significant decline in BMD, an intervening fracture, or other factors that alter the clinical risk status.

Denosumab

  • 3.1 In postmenopausal women with osteoporosis who are at high risk for osteoporotic fractures, ES recommends using denosumab as an alternative initial treatment. (1|⊕⊕⊕⊕)

    Technical Remarks:

    • The recommended dosage is 60 mg subcutaneously every 6 months.
    • The effects of denosumab on bone remodeling, reflected in bone turnover markers, reverse after 6 months if the drug is not taken on schedule. Thus, a drug holiday or treatment interruption are not recommended with this agent.
  • 3.2 In postmenopausal women with osteoporosis who are taking denosumab, ES suggests that the fracture risk be reassessed after 5-10 years and that women who remain at high risk of fractures should either continue denosumab or be treated with other osteoporosis therapies. (2|⊕◯◯◯)
  • 3.3 In postmenopausal women with osteoporosis taking denosumab, administration of denosumab should not be delayed or stopped without subsequent antiresorptive (e.g., bisphosphonates, HT or SERM) or other therapy administered in order to prevent a rebound in bone turnover and to decrease the risk of rapid BMD loss and an increased risk of fracture (UGPS).

Teriparatide and Abaloparatide

  • 4.1 In postmenopausal women with osteoporosis at very high risk of fracture, such as those with severe or multiple vertebral fractures, ES recommends teriparatide or abaloparatide treatment for up to two years for the reduction of vertebral and nonvertebral fractures. (1|⊕⊕⊕)
  • 4.2 In postmenopausal women with osteoporosis who have completed a course of teriparatide or abaloparatide, ES recommends treatment with antiresorptive osteoporosis therapies to maintain bone density gains. (1|⊕⊕◯◯)

Romosozumab

  • A.1 In postmenopausal women with osteoporosis at very high risk of fracture, such as those with severe osteoporosis (i.e., low T-score <-2.5 and fractures) or multiple vertebral fractures, we recommend romosozumab treatment for up to one year for the reduction of vertebral, hip, and nonvertebral fractures. (1|⊕⊕⊕)

    Technical Remarks:

    • The recommended dosage is 210 mg monthly by subcutaneous injection for 12 months.
    • Women at high risk of cardiovascular disease and stroke should not be considered for romosozumab pending further studies on cardiovascular risk associated with this treatment. High risk includes prior myocardial infarction or stroke.
  • A.2 In postmenopausal women with osteoporosis who have completed a course of romosozumab, we recommend treatment with antiresorptive osteoporosis therapies to maintain bone mineral density gains and reduce fracture risk. (1|⊕⊕⊕)

Selective Estrogen Receptor Modulators

  • 5.1 In postmenopausal women with osteoporosis at high risk of fracture and with the patient characteristics below, ES recommends raloxifene or bazedoxifene to reduce the risk of vertebral fractures. (1|⊕⊕⊕⊕)
    • Patient Characteristics:
      • with a low risk of DVT, and
      • for whom bisphosphonates or denosumab are not appropriate, or
      • with a high risk of breast cancer

Menopausal Hormone Therapy and Tibolone

  • 6.1 In postmenopausal women at high risk of fracture and with the patient characteristics below, ES suggests menopausal HT, using estrogen only in women with hysterectomy, to prevent all types of fractures. (2|⊕⊕⊕)
    • Patient Characteristics:
      • Under 60 years of age or <10 years past menopause
      • At low risk of DVT
      • Those in whom bisphosphonates or denosumab are not appropriate
      • With bothersome vasomotor symptoms
      • With additional climacteric symptoms
      • Without contraindications
      • Without prior myocardial infarction or stroke
      • Without breast cancer
      • Willing to take menopausal HT
  • 6.2 In postmenopausal women with osteoporosis at high risk of fracture and with the patient characteristics below, ES suggests tibolone to prevent vertebral and nonvertebral fractures. (2|⊕⊕⊕)
    • Patient Characteristics:
      • Under 60 years of age or <10 years past menopause
      • With a low risk of DVT
      • Those in whom bisphosphonates or denosumab are not appropriate
      • With bothersome vasomotor symptoms
      • With additional climacteric symptoms
      • Without contraindications
      • Without prior myocardial infarction or stroke or high risk for cardiovascular disease
      • Without breast cancer
      • Willing to take tibolone
      • Technical Remark:

      • Tibolone is not available in the U.S. or Canada.

Calcitonin

  • 7.1 In postmenopausal women at high risk of fracture with osteoporosis, ES suggests that nasal spray calcitonin be prescribed only in women who cannot tolerate raloxifene, bisphosphonates, estrogen, denosumab, tibolone, abaloparatide, or teriparatide or for whom these therapies are not considered appropriate. (2|⊕◯◯◯)

Calcium and Vitamin D

  • 8.1 In postmenopausal women with low BMD and at high risk of fractures with osteoporosis, ES suggests that calcium and vitamin D be used as an adjunct to osteoporosis therapies. (2|⊕⊕◯◯)
  • 8.2 In postmenopausal women at high risk of fracture with osteoporosis who cannot tolerate bisphosphonates, estrogen, selective estrogen response modulators, denosumab, tibolone, teriparatide, and abaloparatide, ES recommends daily calcium and vitamin D supplementation to prevent hip fractures. (1|⊕⊕⊕)

Monitoring

  • 9.1 In postmenopausal women with a low BMD and at high risk of fractures who are being treated for osteoporosis, ES suggests monitoring the BMD by DXA at the spine and hip every 1 to 3 years to assess the response to treatment. (2|⊕◯◯◯)

    Technical Remark:

    • Monitoring BTMs (serum CTX for antiresorptive therapy or P1NP for bone anabolic therapy) is an alternative way of identifying poor response or nonadherence to therapy.

Figure 1. Algorithm for the Management of Postmenopausal Women

Grading System

Quality of Evidence
Description of EvidenceHigh QualityModerate QualityLow QualityVery Low Quality
  • Well-performed RCTs
  • Very strong evidence from unbiased observational studies
  • RCTs with some limitations
  • Strong evidence from unbiased observational studies
  • RCTs with serious flaws
  • Some evidence from observational studies
  • Unsystematic clinical observations
  • Very indirect evidence from observational studies
Strength of Recommendation
Strong (1):
“ES recommends…”
Benefits clearly outweigh harms and burdens or vice versa
1|⊕⊕⊕⊕1|⊕⊕⊕1|⊕⊕◯◯1|⊕◯◯◯
Conditional (2):
“ES suggests…”
Benefits closely balanced with harms and burdens
2|⊕⊕⊕⊕2|⊕⊕⊕2|⊕⊕◯◯2|⊕◯◯◯
Ungraded Good Practice StatementUGPS

Abbreviations

BMD, bone mineral density; CTX, C-terminal crosslinking telopeptide; DVT, deep venous thrombosis; DXA, dual-energy X-ray absorptiometry; ES, Endocrine Society; HT, hormone therapy; IV, intravenously; P1NP, procollagen type 1 N-terminal propeptide; PTH, parathyroid hormone; RCT, randomized control trial; SERM, selective estrogen response modulator; VTE, venous thromboembolism

Source

Eastell R, Rosen CJ (chair), Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2019; 104(5):1595-1622

Shoback D, Rosen CJ (chair), Black DM, Cheung AM, Murad MH, Eastell R. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab 2020; doi: 10.1210/clinem/dgaa048

Disclaimer

This pocket guide attempts to define principles of practice that should produce high-quality patient care. It focuses on the needs of primary care practice, but also is applicable to providers at all levels. This pocket guide should not be considered exclusive of other methods of care reasonably directed at obtaining the same results. The ultimate judgment concerning the propriety of any course of conduct must be made by the clinician after consideration of each individual patient situation. Neither IGC, the medical associations, nor the authors endorse any product or service associated with the distributor of this clinical reference tool.