Bisphosphonate Use Is Protective of Radiographic Knee Osteoarthritis Progression Among those With Low Disease Severity and Being Non-Overweight: Data From the Osteoarthritis Initiative

Abstract

Antiresorptive medications have been explored for treating knee osteoarthritis (OA); however, little data exist on the effects of today's more potent nitrogen‐containing oral bisphosphonates on radiographic disease‐progression in patients with varying disease‐severity, especially those who are not overweight. The primary objective of this cohort study was to determine if the use of bisphosphonates is protective against 2‐year radiographic‐progression of knee OA in Osteoarthritis Initiative (OAI) participants, stratified by baseline radiographic disease status. Secondary objectives were to examine effects in non‐overweight participants (body mass index [BMI] < 25 kg/m2) and cumulative bisphosphonate exposure effects. We identified female OAI participants aged ≥50 years and excluded those missing baseline radiograph readings, bisphosphonate use information, or all clinical questionnaire information at baseline. Participants reporting bisphosphonate use (69% alendronate) were propensity‐matched 1:1 to non–bisphosphonate users and followed until first radiographic knee OA progression (1‐unit increase in Kellgren and Lawrence [KL] grade) or data were censored (first missed visit or end of 2‐year follow‐up). Discrete‐time logistic regression models estimated hazard ratios (HRs) between bisphosphonate users versus nonusers, with an interaction term for baseline KL grade (KL <2 or KL ≥2). We identified 1977 eligible women (n = 346 bisphosphonate users). Propensity‐matched results indicated that bisphosphonate users with KL grade <2 were protected against progression (HRKL<2 0.53; 95% CI, 0.35 to 0.79), while bisphosphonate use was not associated with radiographic progression in those with KL grade ≥2 (HRKL≥2 1.06; 95% CI, 0.83 to 1.35). When restricting analyses to those with BMI <25 kg/m2, effects were strengthened (HRKL<2 0.49 [95% CI, 0.26 to 0.92]; HRKL≥2 0.69 [95% CI, 0.33 to 1.26]). Duration of bisphosphonate use had no effect on progression, though sample size was limited. Bisphosphonate therapy may be protective against radiographic knee OA progression in early‐stage patients, particularly those who are non‐overweight, but less so for those with more advanced disease or more weight‐bearing joint stress. © 2020 American Society for Bone and Mineral Research (ASBMR).

Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

“…However, BPs may be suitable for OA patients with high bone turnover (Vaysbrot et al, 2018). A recent report by Hayes et al (2020) suggested an early preventive effect of BPs for a subpopulation of OA patients (Hayes et al, 2020). Hayes et al (2020) identified 346 BP responsive end-users from 1,977 eligible women, and in this cluster of patients, administration of BPs showed a protective effect against radiographic knee OA progression.…”

“…A recent report by Hayes et al (2020) suggested an early preventive effect of BPs for a subpopulation of OA patients (Hayes et al, 2020). Hayes et al (2020) identified 346 BP responsive end-users from 1,977 eligible women, and in this cluster of patients, administration of BPs showed a protective effect against radiographic knee OA progression. The administration of BPs was particularly effective as early prevention for non-overweight patients, but less effective for those with more advanced disease or with higher weight-bearing stress (Hayes et al, 2020).…”

“…Hayes et al (2020) identified 346 BP responsive end-users from 1,977 eligible women, and in this cluster of patients, administration of BPs showed a protective effect against radiographic knee OA progression. The administration of BPs was particularly effective as early prevention for non-overweight patients, but less effective for those with more advanced disease or with higher weight-bearing stress (Hayes et al, 2020). These results suggest that BPs have the potential to be used as a prevention intervention for some early OA patients by regulating subchondral bone remodeling.…”

“…Bone acting agents that are reported to be beneficial for OA patients include estrogen (Carbone et al, 2004), BPs (Carbone et al, 2004;Hayes et al, 2020), and SrR (Reginster et al, 2013;Bruyere et al, 2014). Effective responders to estrogen and BPs are mostly postmenopausal women at early stage of OA, and non-overweight; administration of estrogen or BPs reduced radiographic knee OA progression, and is correlated to less subchondral bone lesions (Carbone et al, 2004;Hayes et al, 2020). Responders to SrR are generally early OA patients from both genders over 50 years old with joint space width 2.5-5 mm from the SEKOIA clinical trial (ISRCTN41323372) (Reginster et al, 2013;Bruyere et al, 2014).…”

Response to: Challenges to the Possible Use of Bisphosphonates in Early-Stage Osteoarthritis

“…We read with interest Zhou and colleagues' response (1) to our article on bisphosphonates' protective effect on knee osteoarthritis progression with data from the Osteoarthritis Initiative. (2) The authors raise important points on methodology and highlight the enthusiasm for examining subchondral bone properties among studies of knee osteoarthritis (OA).…”