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How to treat osteoporosis

Presented by
Prof. Serge Ferrari, Geneva University Hospital, Switzerland
EULAR 2019
Prof. Serge Ferrari (Geneva University Hospital, Switzerland) presented the latest findings and insights into treatment of osteoporosis, monitoring treatment effects, the benefits of preventing fractures, and emerging concepts based on recent publications and evaluation of clinical trials [1].

Osteoporosis therapy is focused on quickly preventing fragility fractures in individuals at risk. Other goals are restoring bone mineral density and, on the longer term, bone strength. Both antiresorptive agents (e.g. zoledronate, denosumab) and anabolics (e.g. teriparatide, romosozumab) have been shown to reduce the risk of vertebral fractures within one year, whereas the benefits on non-vertebral fractures may take about 2 years to appear. “Fracture risk algorithms that combine clinical risk factors and bone mineral density are now widely used in clinical practice to target high-risk individuals for treatment,” said Dr Ferrari. “However, this simple approach has been challenged over the last few years by evidence showing that treating people at intermediate to low-risk would be beneficial as well.”

Prof. Ferrari recommended that treatment sequences should start with anabolics first. The VERO trial compared the efficacy of teriparatide with that of risedronate in reducing the occurrence of new vertebral fractures, during 24 months of therapy in patients with severe osteoporosis. The trial showed that the risk of new vertebral and clinical fractures was significantly lower in patients receiving teriparatide [2]. The FRAME trial demonstrated that romosozumab was linked to a lower risk of vertebral fracture than placebo at 12 months and, after transition to the antiresorptive agent denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year [3].

However, also antiresorptive agents have provided large gains in bone mineral density and rapid fracture risk reduction. The FREEDOM trial demonstrated that denosumab is efficacious in vertebral, hip, and nonvertebral fracture reduction in postmenopausal osteoporosis. While no direct comparisons are available, denosumab appeared to provide a greater reduction in fragility fractures than oral bisphosphonates (e.g. zoledronate) [4]. Also, the GIOP trial assessed the efficacy and safety of denosumab compared with risedronate in glucocorticoid-induced osteoporosis. Denosumab had a positive effect on bone mineral density at the lumbar spine in both glucocorticoid-continuing and glucocorticoid-initiating subpopulations. Safety, including fracture rates, was similar for both treatment groups [5]. Concerning bisphosphonates, Reid et al. showed that the risk of nonvertebral or vertebral fragility fractures was significantly lower in women with osteopenia who received zoledronate compared with women who received placebo. Zoledronate prevented fractures, independent of baseline characteristics such as age, history of fractures and falls, and calculated fracture risk [6,7].

In conclusion, attention is needed for goal-directed osteoporosis treatment. A more aggressive treatment goal may be desirable for patients with a very high baseline risk of fracture, such as those with a recent vertebral fracture or those ≥70 years. It was further mentioned that bone mineral density gain is a good surrogate marker of fracture risk reduction and that it could be used as a future treat-to-target strategy.

  1. Ferrari S. et al. Abstract SP0002. EULAR 2019
  2. Kendler DL, et al. Lancet. 2018 Jan 20;391(10117):230-240.
  3. Cosman F, et al. N Engl J Med. 2016 Oct 20;375(16):1532-1543.
  4. Cummings SR, et al. N Engl J Med. 2009 Aug 20;361(8):756-65.
  5. Saag KG, et al. Lancet Diabetes Endocrinol. 2018 Jun;6(6):445-454.
  6. Reid IR, et al. N Engl J Med. 2018 Dec 20;379(25):2407-2416.
  7. Reid IR, et al. J Intern Med. 2019 Mar 18.

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