Updates in osteoporosis: the 2019 Endocrine Society Clinical Practice Guidelines

Updates in osteoporosis: the 2019 Endocrine Society Clinical Practice Guidelines   

Meg Tapp, PharmD, Essentia Health 

Background: Osteoporosis is a debilitating disease, and 50% of postmenopausal women will experience at least one osteoporotic fracture in their lifetime. Fortunately, there is an array of safe and effective treatments available to improve bone density in women with osteoporosis. These medications are often underused; in recent years bisphosphonate use in the United States has decreased. The Endocrine Society recognized the need for updated guidance, and published recommendations based on a meta-analysis of 106 randomized controlled trials involving 193,987 women. These guidelines have several distinctions from previously published American College of Physicians (ACP) and National Osteoporosis Foundation (NOF) guidelines.

Evidence: In the United States, pharmacological therapy for osteoporosis is indicated for postmenopausal women with history of hip or vertebral fracture; T-score of -2.5 or less at the femoral neck, hip, or lumbar spine; or T-score of -1 to -1.25 plus FRAX score of >/= 20% for major fractures or >/= 3% for hip fractures. The Endocrine Society recommends treatment for all women meeting these criteria, regardless of age and especially if they have had a fracture in the past two years. Contrary to ACP guidelines, the Endocrine Society recommends bone mineral density (BMD) monitoring every one to three years during treatment.

Similar to ACP and NOF guidelines, the Endocrine Society recommends bisphosphonates or denosumab as first-line treatment for osteoporosis. While ACP has the same drug holiday recommendations for both drug classes, these new guidelines suggest reassessing bisphosphonate use after five years (three years for zoledronic acid) and denosumab use after 5-10 years. Patients who remain at high risk for fractures should continue therapy. If a drug holiday is pursued, BMD should be monitored every two to four years post-bisphosphonate and every one to three years post-denosumab. If denosumab is stopped, a bisphosphonate should be used to prevent rapid bone loss. For either drug class, therapy should be resumed if there is loss in BMD or a fracture occurs.

Teriparatide and abaloparatide have their place in all guidelines for women with severe or multiple fractures; they may be used for up to two years and followed by anti-resorptive therapy. Older guidelines have moved away from the use of raloxifene, hormone replacement therapy, and calcitonin, but the Endocrine Society does recommend these medications as second-line therapy for women with specific indications. Raloxifene may be used in patients with low risk for deep vein thrombosis (DVT) and high risk for breast cancer. Hormone replacement therapy should only be used for patients with low risk of DVT, stroke, or myocardial infarction with no history of breast cancer and who are <60 years of age or <10 years post-menopause. Calcitonin is reserved as a last-line therapy.

The Endocrine Society guidelines are unique in that they are the first osteoporosis guidelines to include women’s preferences regarding treatment options. Results from a meta-analysis of 15,348 postmenopausal (Barrionuevo et al.) concluded women consider efficacy and adverse effects top priority, followed by convenience; overall the oral route was preferred unless injections were less frequent. Surprisingly, cost and duration of treatment were the least important considerations.

Discussion and Clinical Impact: While many recommendations in the Endocrine Society guidelines are similar to ACP and NOF guidelines, there are several key differences. ACP removed BMD monitoring from their recommendations; the Endocrine Society re-introduces monitoring every one to three years. Bisphosphonates and denosumab are still preferred first-line agents; however, recommendations for duration of treatment and initiation of drug holidays differ. The Endocrine Society Clinical Practice guidelines also resurrect specific recommendations for hormone replacement therapy, raloxifene, and calcitonin. This provides for an expanded range of options for many women who cannot tolerate first-line medications. 

The Endocrine Society guidelines provide insight into the most important factors affecting therapy choice for osteoporotic women - namely efficacy, safety, and convenience. Such information can be used to guide patients through discussions regarding their treatment options, and should be kept in mind when making therapeutic recommendations.

References:   

  1. Eastell R, Rosen CJ, 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.   

  2. Barrionuevo P, Gionfriddo MR, Castaneda-Guarderas A, et al. Women’s values and preferences regarding osteoporosis treatment: a systematic review. J Clin Endocrinol Metab. 2019; 104(5):1631-1636.