Denosumab Treatment Improves Health‐Related Quality of Life in Osteoporosis: Is It Still an Attractive Topic?

Abstract

In a recent prospective cohort study, Hayashi and colleagues (1) assessed the effectiveness of denosumab in improving healthrelated quality of life (HRQoL) in osteoporotic patients, reporting not only that this drug would be useful in reducing pain and improving quality of life, but that these effects could be correlated to a BMD increase. However, although we agree with the authors' conclusions, there are two questionable issues regarding this study, in light of findings reported in our recent publication on a similar topic. (2) Clinically, osteoporosis itself is not a painful condition, except in the case of fragility fractures. (3) These fractures typically cause acute nociceptive pain that begins immediately after the trauma and lasts until bone-healing occurs. The presence of persistent pain after osteoporotic fractures results mainly from two mechanisms: the failure of fracture healing (eg, pseudoarthrosis) occurring in a varied percentage of patients (15% to 35%) (4) or from biomechanical modifications that stimulate pain-sensitive structures of the spine (ie, facet joint capsules and ligaments). Finally, vertebral fragility fractures may cause chronic pain as a result of peripheral and/or central sensitization mechanisms, (5) with a consequently huge impact on activities of daily living, social participation, and economic burden, as well as HRQoL. (6) It is not surprising that in the cohort included by Hayashi and colleagues (1) over 50% of patients had prevalent fragility fractures, of which more than 70% occurred at the spine, although the authors did not adequately enhance this data.In our real-practice prospective study, (2) denosumab was significantly effective in both reducing back-pain-related disability and improving HRQoL, as assessed by two validated and widely used outcome measures, the 12-Item Short Form Health Survey (SF-12) and the European Quality of Life-5 Dimensions-3 Levels (EuroQol-5D-3L), in osteoporotic postmenopausal women with vertebral fractures in long-term follow-up (1 year), with significant benefits reported at 6 months after the injection in all outcomes investigated.In addition, the measurement of BMD at the distal radius to assess the effectiveness of denosumab in terms of bone density changes, and to correlate BMD measured at that skeletal site with pain and quality of life, seems somehow questionable. Indeed, the recommended sites for the diagnosis of osteoporosis proposed by the International Society for Clinical Densitometry (ISCD), (7) the sites that were also used in the denosumab pivotal trial, (8) are the lumbar spine, femoral neck, and total hip. However, the phase 3 randomized FREEDOM trial and open-label extension (9) demonstrated that the long-term use of denosumab is able to significantly increase the BMD at one-third radius both in osteoporotic patients treated for 10 years (long-term group) and in those transitioned to denosumab after having received placebo for the first 3 years (crossover group) by 2.7% and 2.3%, respectively. Nevertheless, the ISCD recommen...