Friday, 19 Jul 2019

You are here

Benefits vs Harms for Osteoporosis Drug Continuation or Discontinuation

While it is clear that long-term bisphosphonate therapies reduce fracture risk in women with osteoporosis, it is unclear how to counter-balance these benefits against rare serious harms and how to optimize therapeutic benefits with appropriate drug holidays.

A systematic analysis of 48 studies compared long-term osteoporosis drug treatment (ODT) (>3 years) versus control versus ODT continuation versus durg discontinuation, to examine incident fractures or harms.

In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate strength of evidence - SOE).

Long-term bisphosphonates showed an increased risk for atypical femoral fractures and osteonecrosis of the jaw (both low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapy reduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms.

After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE).

Trials and data in men with clinical fracture data were sparse.

No trials compared sequential treatments or different durations of drug holidays.

It appears that long-term bisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may also reduce the risk for fractures.

Until there are well designed trials informing us on the magnitude of benefit vs. risk with drug holidays of varying duration, the decision to continue or discontinue ODT must be based on the individuals risk for future fracture. 

Disclosures: 
The author has no conflicts of interest to disclose related to this subject

Add new comment

More Like This

Intraarticular Capsaicin in Knee Osteoarthritis

A novel compound, synthetic trans‐capsaicin (CNTX‐4975), has been studied as an intraarticular injection and shown to significantly reduce pain in patients with chronic moderate‐to‐severe osteoarthritis of the knee. A phase II, multicenter, double‐blind study enrolled 172 knee OA patients between the ages of 45–80 years. Patients were randomized to receive either intraarticular placebo, or a high‐purity synthetic trans‐capsaicin CNTX‐4975 0.5 mg, or CNTX‐4975 1.0 mg.

Increased Risk of Cardiovascular Death in Hip and Knee Osteoarthritis

Hip and knee osteoarthritis patients have been shown to have increased mortality rates from cardiovascular events when compared to the general population.

The study included patients in the Skåne Healthcare Register from southern Sweden who were 45–84 years old and seen over 2004-2014. Overall, there were 15,901 such patients in the study.

Safety Concerns Offset the Modest Improvements of Tanezumab in Osteoarthritis

JAMA reports that although tanezumab is modestly effective in moderate to severe osteoarthritis (knee or hip), with statistically significant improvements in pain and physical function, the tanezumab (TNZ) treated patients had more joint safety events and total joint replacements than patients treated with placebo.

Mortality from Falls in the Elderly

JAMA reports that there is a trend of increasing mortality from falls in older US adults between 2000 to 2016 and that mortality rates are increased with increasing age. 

Knee Injuries Increases Osteoarthritis Risk

A systematic review of the medical literature shows anterior cruciate ligament (ACL), meniscus or combined ACL and meniscus injury significantly increases the risk of future knee osteoarthritis (OA).

The metanalysis comprised 53 studies and nearly 1 million participants, including 185,219 with ACL injury (mean age 28 years), 83,267 with meniscal injury (mean 38 years) and 725,362 with combined injury (mean 31 years).