Full Guideline: Pharmacological Management of Osteoporosis in Postmenopausal Women
JCEM: May 2019 (online March 2019)
Richard Eastell, Clifford J. Rosen (chair), Dennis M. Black, Angela M. Cheung, M. Hassan Murad, and Dolores Shoback
Guideline Update: Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update
JCEM: March 2020 (online February 2020)
Dolores Shoback, Clifford J. Rosen (chair), Dennis M. Black, Angela M. Cheung, M. Hassan Murad, and Richard Eastell
The guideline on pharmacological management of osteoporosis in postmenopausal women:
- Provides recommendations for the treatment and management of osteoporosis in postmenopausal women
- Emphasizes assessment after being on treatments to see if further treatment is necessary
Resources
Guideline Introduction | ENDO 2019
Essential 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.
List of Recommendations
+ 1.0 Who to Treat
- 1.1 We recommend 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|⊕⊕⊕⊕)
+ 2.0 Bisphosphonates
- 2.1 In postmenopausal women at high risk of fractures, we recommend 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, we recommend that fracture risk be reassessed after 3-5 years, and women who remain at high risk of fractures should continue therapy, whereas 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 bone mineral density 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 research control trials 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 bone mineral density, an intervening fracture, or other factors that alter the clinical risk status.
+ 3.0 Denosumab
- 3.1 In postmenopausal women with osteoporosis who are at high risk for osteoporotic fractures, we recommend 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, we suggest 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., bisphosphonate, hormone therapy or selective estrogen receptor modulator) or other therapy administered in order to prevent a rebound in bone turnover and to decrease the risk of rapid bone mineral density loss and an increased risk of fracture (Ungraded Good Practice Statement).
+ 4.0 Teriparatide and Abaloparatide—Parathyroid Hormone and Parathyroid Hormone-Related Protein (PTHrP) Analogs
- 4.1 In postmenopausal women with osteoporosis at very high risk of fracture, such as those with severe or multiple vertebral fractures, we recommend 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, we recommend treatment with antiresorptive osteoporosis therapies to maintain bone density gains. (1|⊕⊕⚪⚪)
+ Update A (2020). 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 or 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|⊕⊕⊕⚪)
+ 5.0 Selective Estrogen Receptor Modulators
- 5.1. In postmenopausal women with osteoporosis at high risk of fracture and with the patient characteristics below, we recommend raloxifene or bazedoxifene to reduce the risk of vertebral fractures. (1|⊕⊕⊕⊕)
Patient Characteristics:
- with a low risk of deep vein thrombosis and
- for whom bisphosphonates or denosumab are not appropriate or
- with a high risk of breast cancer
+ 6.0 Menopausal Hormone Therapy and Tibolone
- 6.1 In postmenopausal women at high risk of fracture and with the patient characteristics below, we suggest menopausal hormone therapy, 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 deep vein thrombosis
- 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 hormone therapy
- 6.2 In postmenopausal women with osteoporosis at high risk of fracture and with the patient characteristics below, we suggest 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 deep vein thrombosis
- 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.
+ 7.0 Calcitonin
- 7.1 In postmenopausal women at high risk of fracture with osteoporosis, we suggest 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|⊕⚪⚪⚪)
+ 8.0 Calcium and Vitamin D
- 8.1 In postmenopausal women with low bone mineral density and at high risk of fractures with osteoporosis, we suggest 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, we recommend daily calcium and vitamin D supplementation to prevent hip fractures. (1|⊕⊕⊕⚪)
+ 11.0 Monitoring
- 11.1 In postmenopausal women with a low bone mineral density and at high risk of fractures who are being treated for osteoporosis, we suggest monitoring the bone mineral density by dual-energy X-ray absorptiometry at the spine and hip every 1 to 3 years to assess the response to treatment. (2|⊕⚪⚪⚪)
Technical Remark: Monitoring bone turnover markers (serum C-terminal crosslinking telopeptide for antiresorptive therapy or procollagen type N-terminal propeptide for bone anabolic therapy) is an alternative way of identifying poor response or nonadherence to therapy.
