Effect of bisphosphonate use in patients with symptomatic and radiographic knee osteoarthritis: data from the Osteoarthritis Initiative

Abstract

Objectives: Bisphosphonates have some reported beneficial effects in treating osteoarthritis (OA). This study examined the effects of bisphosphonate use on symptoms and structural progression of knee OA in participants from the NIH Osteoarthritis Initiative cohort. Methods:People with typical OA trial entry criteria (KL2/3, minimum joint space width (mJSW) 2.5-5.0mm and pain ≥4 on a numerical rating scale [NRS]) were classified as bisphosphonate users (3 of the 5 years; n=55) or non-users (no use in the preceding 5 years or during follow-up; n=268). Annual data over 4 years were analysed using linear mixed modelling and generalised estimating equations.Results: Bisphosphonate compliance was 85% at year 1, reducing to 76% by year 4. NRS pain scores were significantly reduced among bisphosphonate users at years 2 and 3 (Year 3, -0.9 vs -2.2, p=0.004), though not year 4, after adjustment for baseline pain and analgesic use. Differences in WOMAC pain and disability scores did not reach statistical significance at any time point. There was a trend to less joint space narrowing in bisphosphonate users over time (Year 4, 0.51mm vs 0.29mm; p=0.06). Zoledronic acid has been reported effective in reducing knee pain and the size of BMLs. Conclusions[7]However, though risedronate (15 mg) reduced markers of cartilage degradation and bone resorption, it did not achieve WOMAC symptom reduction or slowing of radiologic progression of joint space narrowing over 2 years [19,20]. Page 4The NIH Osteoarthritis Initiative (OAI) provides a large, comprehensive dataset which permits exploration of the effects of bisphosphonates over a number of years.We aimed to examine the effect of bisphosphonate use on OA symptom and structural outcomes in people selected from the OAI cohort for typical OA trial inclusion criteria and followed for 4 years. PATIENTS AND METHODS Study design, setting and participantsData used in the preparation of this article were obtained from the Osteoarthritis Initiative (OAI) cohort, a publicly available multi-centre population-based observational cohort study of knee OA which is available for public access at http://www.oai.ucsf.edu/. Specific datasets used are detailed Supplementary Table 1. The OAI comprises data on persons aged 45-79 years within three sub-cohorts, the Progression group (persons with existing knee OA; n=1,390), the Incidence group (persons with risk factors for knee OA; n=3,284) and the non-exposed control group (n=122) [21]. Both knees of 4796 participants were studied annually using 3T MR imaging (not used in these analyses) and fixed flexion radiography [22,23]at baseline, 1, 2, 3 and 4 years follow-up.Persons were excluded from the OAI if they had inflammatory arthritis, severe joint space narrowing (JSN) in both knees, unilateral knee joint replacement and severe JSN in the contralateral knee, inability to undergo MRI, or to provide a blood sample, required use of walking aids excepting a single straight cane ≤50% of the time, or were unwilling to provide informed consent. Pat...

Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression

“…After six weeks of OA induction both groups showed no difference in macrophage activation, however, after 12 weeks macrophage activation was significantly reduced in ALN treated animals compared to untreated animals. Recently, bisphosphonates have been reported to significantly reduce pain in patients with clinical and radiographic knee osteoarthritis [45]. Synovitis and activation of synovial macrophages are related to patient complaints, like joint dysfunction and pain [46], and has been related to the progression of cartilage erosion [47,48].…”

Drugs and Polymers for Delivery Systems in OA Joints: Clinical Needs and Opportunities

“…These positive results are promising for the application of peptidal DMOADs in a DDS. Even DMOADs and drugs that can be administered systemically or by injection (bisphosphonates and Platelet-rich plasma (PRP) respectively) seem to benefit from a DDS [58,59]. These results also suggest that there might be a beneficial effect of targeting subchondral bone in OA treatment, but more evidence is needed, especially in drug delivery systems.…”

An OA phenotype may obtain major benefit from bone-acting agents

“…In a recent study, the use of bisphosphonates, predominantly alendronate, by 3-5 years showed beneficial effects in treating knee OA [62]. This longitudinal study demonstrated reduction in numeric rating scale pain in the first 3 years with bisphosphonate use, although diminution of effects was observed by year 4 likely reflecting reduced compliance.…”

“…This longitudinal study demonstrated reduction in numeric rating scale pain in the first 3 years with bisphosphonate use, although diminution of effects was observed by year 4 likely reflecting reduced compliance. There were also differences in radiological progressors and a trend to reduction of joint space narrowing in bisphosphonate users over time [62]. In a previous study, elderly women treated with alendronate had less severity of knee pain, as assessed by WOMAC scores, and decreased prevalence of knee OA-related subchondral bone lesions compared with those reporting no use [51].…”