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Positive effect denosumab on fall risk

Presented by
Dr Yasser El Miedany, Darent Valley Hospital, United Kingdom
EULAR 2020
Osteoporosis is strongly associated with skeletal muscle dysfunction [1]. A recent study found that treatment with denosumab improved physical performances, grip strength, and gait speed outcomes, and thus appears to reduce the risk of falling for osteoporosis patients.

Heparan-sulphate proteoglycans are abundant in skeletal muscles and may represent a target for receptor activator of nuclear factor-kB (RANKL) inhibitor, such as denosumab. Thus, Dr Yasser El Miedany (Darent Valley Hospital, United Kingdom) and colleagues set out to investigate the effect of denosumab on fall risk, physical performance, grip strength, and gait speed, and whether a relationship exists with bone mineral density (BMD) [1]. This was done by assessing 127 osteoporotic patients at the start of treatment with denosumab and again after 5 years. The investigators assessed baseline BMD (measured by dual X-ray absorptiometry), the patients’ osteoporosis bone profile by means of a blood test, the self-reported Falls Risk Assessment Score (FRAS), the Fracture Risk Assessment Tool (FRAX), and handgrip strength using a calibrated dynamometer (the best of 3 trials of the dynamometer testing was recorded) [2]. The patient’s physical performance was assessed by testing for Short Physical Performance Battery (SPPB), Timed Up and Go (TUG), and the 4 Meter Walk Gait Speed. Comparison groups included 112 osteoporosis patients who were treated with zoledronate (once yearly IV injection) for 3 years, and a group of 134 patients who were treated with once-weekly oral alendronate 70 mg for 5 years. The patients in both comparison groups were assessed for the same parameters as those who were treated with denosumab. All measures were reassessed 1 year after stopping osteoporosis therapy. No differences were found when comparing the baseline parameters of the 3 groups.

Compared with baseline, a significant increase in BMD was observed in all 3 groups at both the spine and the hip (P=0.02) at 1, 3, and 5 years of denosumab/zoledronate/alendronate treatment, respectively [1]. At 5 years, a significant decrease was observed in the denosumab group in falls risk score (-1.4; 95% CI −2.8 to −0.7; P=0.01), as well as significant improvements in the grip strength (+4.2 kg; P=0.01), SPPB score (+1.2 points; 95% CI −0.07 to 2.2; P=0.02), TUG (+1.7 seconds; 95% CI -2.2 to 0.1; P=0.031), and gait speed (+0.1 m/s; 95% CI 0.03 to 0.2; P=0.01). Zoledronate and alendronate significantly improved the SPPB score (+0.9 and +0.8 points, respectively; P=0.04), TUG (+1.4 and +1.3 seconds, respectively; P=0.05), and gait speed (+0.2 and +0.3 m/s, respectively; P=0.02). No significant change in fall risk was observed (P=0.06 and P=0.07, respectively). One year after stopping treatment with denosumab, researchers noticed a significant worsening of the fall risk score, grip strength, SPPB score, TUG, and gait speed (P=0.1). No difference was seen in all measures 1 year after stopping zoledronate and alendronate. Additionally, no relation was observed to the increase in BMD gained.

Thus, the investigators concluded that denosumab displayed a positive impact and significant improvements in physical performance, grip strength, and gait speed, as well as enhancing multidirectional agility as depicted by TUG. Collectively, this would help explain the reduction of falls risk, which got worse on stopping the medication. Osteoporosis and sarcopenia share similar risk factors, highlighting muscle-bone interactions, which may result in debilitating consequences, such as falls and fractures.

  1. El Miedany Y, et al. Abstract OP0313. EULAR E-Congress, 3-6 June 2020.
  2. El Miedany Y, et al. J Clin Gerontology and Geriatrics. 2011; 21-26.


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