New osteoporosis guideline: Who to treat with what
A new osteoporosis guideline by the Endocrine Society puts a premium on women at high risk of fractures, particularly those who have had a recent fracture after menopause, and outlines the latest pharmacologic options for specific patient groups.
One in two postmenopausal women will break a bone in their lifetime due to osteoporosis, and those who have had a fracture are at a higher risk for subsequent fractures, said Dr Clifford Rosen, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute in Scarborough, US and chair of the guideline writing committee. “However, many women at the highest risk do not receive treatment. We need to be aggressive about treating those who have had a previous fracture.”
Prior to initiating therapy, lifestyle and nutritional interventions – including supplementation with calcium and vitamin D – as well as fall prevention measures, are recommended, together with assessment of 10-year fracture risk according to country-specific guidelines.
Bisphosphonates and denosumab remain to be the first-line therapies, with a reminder that fracture risk should be reassessed after 3–5 years in those who have been on bisphosphonates. Women who remain at high risk of fractures despite being on bisphosphonates should continue therapy. Those on low risk should be considered for a bisphosphonate holiday for up to 5 years. Ibandronate is not recommended to reduce nonvertebral or hip fracture risk though. [J Clin Endocrinol Metab 2019;104:1595-1622]
No denosumab holiday
Denosumab is specifically recommended for postmenopausal women with osteoporosis who are at high risk for osteoporotic fractures, at a dosing of 60 mg subcutaneously every 6 months. If not taken as directed, denosumab effect on bone remodeling reverses after 6 months. Hence, a drug holiday or treatment cessation is not recommended with denosumab, said Rosen.
Fracture risk should be reassessed after 5–10 years of being on denosumab to assess if there is a need to continue with the drug or switch to other osteoporosis therapies. In those taking denosumab, treatment should not be delayed or stopped without subsequent antiresorptive to prevent a rebound in bone turnover and to decrease the risk of rapid bone mineral density (BMD) loss.
Other therapeutic options
For postmenopausal women with osteoporosis at high risk of fractures, or with a history of severe or multiple vertebral fractures, the Endocrine Society recommends anabolic treatments with teriparatide or abaloparatide for up to 2 years. In those who completed a course of either teriparatide or abaloparatide, antiresorptive therapies are advised to maintain bone density gains.
Raloxifene or bazedoxifene can be considered in women with a low risk of deep vein thrombosis (DVT) and those for whom bisphosphonates or denosumab are inappropriate, or in those with a high risk of breast cancer. Menopausal hormone therapy may be considered in those 60 years and younger or <10 years past menopause, with low risk of DVT, and in whom bisphosphonates or denosumab are not appropriate, with bothersome vasomotor symptoms and additional climacteric symptoms, without contraindications, prior MI, stroke, or breast cancer. Estrogen treatment is advised only for women with hysterectomy at high risk for fracture.
Calcitonin nasal spray may be considered in women who cannot tolerate or for whom the aforementioned therapies are not considered appropriate. Calcium and vitamin D, either in diet or via supplements, should be used as an adjunct osteoporosis therapy.
For women with low BMD and at high risk of fractures, monitoring of the BMD at the spine and hip every 1 –3 years is advised to assess treatment response.
Current treatment gap
“Pharmacologic therapies could reduce fracture rates in postmenopausal women at risk, with acceptable risk-benefit and safety profiles,” said Rosen. “But then currently, there is a considerable gap in treatment.”
He even acknowledged some concerns about the risk of atypical femoral fracture (AFF) that has been linked to bisphosphonates. Often, patients ask why they should take medicines that are meant to prevent fractures but may cause another type of fracture, Rosen said. “From a physician standpoint, it’s hard because you have to spend time to discuss absolute risk and relative risk differences with each individual patient. And you’ve to know what a patient’s perception of risk is, and how fearful she is … that takes time, hence, many are reluctant to treat.”
This in effect has resulted in fewer prescriptions for osteoporosis. “We have not been treating enough. Seven of 10 who started on medicines have dropped within a year after initiation. Even bone density screening has declined precipitously. It’s a dilemma as we need to treat these women.”
Though recent data suggest that the risk of AFF with bisphosphonates remains low, Rosen acknowledged that there may be an increased risk with long-term therapy. Hence, the recommendation for a drug holiday with bisphosphonates after 3-5 years of taking it.
“We hope our guideline will not only improve patient care but provide confidence in treatment. Patient preferences, however, should be incorporated into treatment planning.”
The new guideline is more targeted and detailed compared to the 2017 American College of Physicians (ACP) guideline, where drug therapy for 5 years is advised but does not differentiate between bisphosphonates and denosumab in terms of treatment duration.