Need to quickly get up to speed on the osteoporosis field? I’ve chosen the twelve clinical papers that I think will have the greatest clinical impact, and why I think they’re significant.
- Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial.
This paper shows that the strong fracture reductions observed in the ACTIVE trial for Radius Health’s Tymlos (abaloparatide) are maintained when those patients switch to alendronate, demonstrating the applicability of sequential therapy. Radius Health will hope these results convince patients, physicians, and payers as well.
Amgen/UCB were hoping to demonstrate Evenity’s (romosozumab) superior fracture reduction against alendronate. They achieved this, but unfortunately also uncovered a cardiovascular signal that has delayed regulatory approval. These findings could result in restrictions on Evenity’s use or stop its launch altogether. There’s also an excellent authors’ responses to comments article here.
- Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial.
This paper showed superior increases in bone mineral density (BMD) in Evenity versus Eli Lilly’s Forteo (teriparatide), in patients who had previously been treated with bisphosphonates – a clinically common scenario. If Evenity is approved, these data may support use of certain anabolic agents in different patient groups.
This retrospective cohort study examined the cardiovascular events that occurred in patients who had suffered a hip fracture. The authors found alendronate treatment significantly decreased a patient’s risk of cardiovascular events. These results may prove crucial when assessing romosozumab’s safety.
- Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.
This was the first clinical trial with sufficient statistical power to compare two osteoporosis therapies with clinical fracture as the primary endpoint. It demonstrated Forteo’s superiority to a bisphosphonate in reducing the risk of new vertebral and clinical fractures, and gives Eli Lilly powerful evidence to convince reluctant payers of Forteo’s effectiveness.
- 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension.
The FREEDOM trial showed that Prolia (denosumab)-treated patients continue to see increases in BMD with extended treatment. Additionally, the long-term safety and efficacy in reducing the risk of risk was demonstrated, adding reassurance to Prolia-treated patients.
The authors of this paper found that stopping Prolia without an alternative osteoporosis-treatment resulted in a reversal of BMD gains, the so called ‘a rebound effect’. It highlights the need for physicians to plan therapeutic alternatives if Prolia treatment stops.
- Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study.
Patients treated with glucocorticoids are at a significantly increased risk of sustaining a fragility fracture, caused by glucocorticoid-induced osteoporosis (GIOP). This trial demonstrated Prolia’s superiority versus risedronate in efficacy, with the data used in Amgen’s successful label expansion in GIOP patients.
- Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials.
Previous studies have shown the increased risk of cardiovascular disease and breast cancer in HRT-treated women. This long-term follow-up casts doubt on these results, showing no associated risk of all-cause, cardiovascular, or cancer mortality, and should reassure those patients of HRT’s safety.
- Screening in the community to reduce fractures in older women (SCOOP): a randomised controlled trial.
Diagnosis and treatment rates for osteoporosis are stubbornly low. In this paper the authors used FRAX to identify patients’ risk of sustaining a fracture. They found it particularly effective in reducing hip fractures, one of the most debilitating consequences of osteoporosis.
- Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance.
Atypical femoral fracture (AFF) is an extremely rare, but serious, possible side effect of bisphosphonate use that has caused a significant drop in diagnosis and treatment rates. The authors of this paper found a possible mechanism that may not necessarily reassure patients – bisphopsphonates treated bones are weaker – but at least gives a possible explanation to the cause of AFF.
- Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older Adults: A Systematic Review and Meta-analysis.
How effective Vitamin D and calcium supplementation are in reducing fractures is fiercely debated by both sides of the argument. This paper concluded that the routine use of these supplements in community-dwelling older people was not beneficial. We expect this debate to continue.
DRG’s Osteoporosis Disease Landscape & Forecast provides comprehensive market intelligence providing world-class epidemiology, keen insight into current treatment paradigms, in-depth pipeline assessments, and drug forecasts supported by detailed primary and secondary research.