17 October, 2016:
The American Association of Clinical Endocrinologists and the American College of Endocrinology recently updated their guidelines for the diagnosis and treatment of postmenopausal osteoporosis [1]. These guidelines are presented in a very methodological way, with answers to common core questions. While the full text can be seen in the link below, I decided to pick only the recommendations which seem the most important or bring some new insights. Each statement is graded (in brackets). The article includes a clear and simple treatment algorithm as well.
How is fracture risk assessed and osteoporosis diagnosed?
Evaluate all postmenopausal women aged ≥ 50 years for osteoporosis risk (Grade B; downgraded due to gaps in evidence).
Osteoporosis should be diagnosed based on the presence of fragility fractures in the absence of other metabolic bone disorders (Grade B) or a T-score of −2.5 or lower in the lumbar spine, femoral neck, total hip, and/or one-third radius even in the absence of a prevalent fracture (Grade B).
Osteoporosis may also be diagnosed in patients with osteopenia and increased fracture risk using FRAX® country-specific thresholds (Grade B).
What are the fundamental measures for bone health?
Maintain serum 25-hydroxyvitamin D (25(OH)D) ≥ 30 ng/ml in patients with osteoporosis (preferable range, 30–50 ng/ml) (Grade B, upgraded based on expert consensus).
Supplement with vitamin D3 if needed; 1000–2000 IU of daily maintenance therapy is typically needed to maintain an optimal serum 25(OH)D level (Grade C, upgraded based on expert consensus).
Counsel patients to maintain adequate dietary intake of calcium, to a total intake (including diet plus supplement, if needed) of 1200 mg/day for women ≥ 50 years (Grade B).
Who needs pharmacologic therapy?
Strongly recommend pharmacologic therapy for patients with osteopenia or low bone mass and a history of fragility fracture of the hip or spine (Grade A).
Strongly recommend pharmacologic therapy for patients with a T-score of −2.5 or lower in the spine, femoral neck, total hip or one-third radius (Grade A).
Strongly recommend pharmacologic therapy for patients with a T-score between −1.0 and −2.5 if the FRAX® 10-year probability for major osteoporotic fracture is ≥ 20% or the 10-year probability of hip fracture is ≥ 3% in the US or above the country-specific threshold in other countries or regions (Grade B).
What medication should be used to treat osteoporosis?
[Pay attention to the fact that, for these societies, postmenopausal hormone therapy is not a therapeutic option. Amos Pines].
Approved agents with efficacy to reduce hip, non-vertebral, and spine fractures including alendronate, risedronate, zoledronic acid, and denosumab are appropriate as initial therapy for most patients at high risk of fracture (Grade A).
Teriparatide, denosumab, or zoledronic acid should be considered for patients unable to use oral therapy and as initial therapy for patients at especially high fracture risk (Grade A).
Raloxifene or ibandronate may be appropriate initial therapy in some cases where patients require drugs with spine-specific efficacy (Grade A).
How is treatment monitored?
Obtain a baseline axial (spine and hip) DXA, and repeat DXA every 1–2 years until findings are stable. Continue with follow-up DXA every 1–2 years or at a less frequent interval, depending on clinical circumstances (Grade B).
Follow-up of patients should ideally be conducted in the same facility with the same machine (Grade B, upgraded based on expert consensus).
Significant reductions in bone turnover markers are seen with antiresorptive therapy and have been associated with fracture reduction; significant increases indicate good response to anabolic therapy (Grade B, downgraded based on expert consensus).
What is successful treatment of osteoporosis?
Successful treatment of osteoporosis is defined as stable or increasing bone mineral density with no evidence of new fractures or fracture progression (Grade A).
Consider alternative therapy or reassessment for causes of secondary osteoporosis in patients who have recurrent fractures or significant bone loss while on therapy (Grade A). A single fracture while on therapy is not necessarily evidence of treatment failure, but it does suggest that fracture risk is high.
How long should patients be treated?
For oral bisphosphonates, consider a 'bisphosphonate holiday' after 5 years of stability in moderate-risk patients (Grade B, downgraded due to limitations of data); consider a 'bisphosphonate holiday' after 6–10 years of stability in higher-risk patients (Grade B, downgraded due to limitations of data).
For intravenous zoledronic acid, consider a drug holiday after three annual doses in moderate-risk patients and after six annual doses in higher-risk patients (Grade B, downgraded due to limitations of data).
The ending of the 'holiday' for bisphosphonate treatment should be based on individual patient circumstances (fracture risk or change in bone mineral density or bone turnover markers) (Grade B, upgraded based on expert consensus).
Is combination therapy better than treatment with a single agent?
Until the effect of combination therapy on fracture risk is demonstrated, AACE does not recommend concomitant use of these agents for prevention or treatment of postmenopausal osteoporosis (Grade C, expert consensus, upgraded due to cost and potential increased side-effects).
If estrogen is being given for treatment of menopausal symptoms or raloxifene is administered to reduce the risk of breast cancer, an additional agent such as a bisphosphonate, denosumab, or teriparatide may be considered in higher-rise patients (Grade D).
Treatment with teriparatide should always be followed by antiresorptive agents to prevent bone density decline and loss of fracture efficacy (Grade A).
Comment
I found intriguing the following recommendations, which, I guess, in many countries are not in line with local reimbursement guidelines: One may treat mild osteopenic women (T-score above -1.0) if at high risk according to FRAX score for 10-year fracture risk.
Raloxifene is advised only when the increased fracture risk relates to the spine.
Denosumab is included among first-line therapies.
If treated, monitoring of DXA values is advised every 1–2 years until stabilization and even later on during follow-up.
Once again, estrogen is not included in the list of potential medications, despite its approved osteoporosis indication, and the huge database that support its efficacy in prevention of spine, hip and all-site fractures.
Amos Pines
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
References
1. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis, 2016. Executive summary. Endocr Pract 2016;22:1111-18
