Alendronate treatment for hip osteoarthritis: prospective randomized 2-year trial

Abstract

We examined the clinical efficacy of alendronate treatment for hip osteoarthritis using multiple outcome measures. Fifty patients with symptomatic hip osteoarthritis were enrolled in this prospective trial. The patients were randomly assigned to an alendronate group (35 mg/week alendronate and 600 mg/day calcium lactate) or a control group (600 mg/day calcium lactate) for 2 years. The groups were compared with regard to the following five parameters. The primary outcome measures are the following: (1) the Western Ontario and McMaster Universities (WOMAC) osteoarthritis pain score and the visual analog score (VAS). The secondary outcome measures are the following: (2) joint space width (JSW) measured on radiographs using a semiautomatic computer software, (3) the biochemical markers urinary N-telopeptide of type I collagen (NTX-I) and C-terminal cross-linking telopeptide of type II collagen (CTX-II), (4) dual-energy X-ray absorptiometry of the hip and lumbar spine, and (5) bone marrow edema on magnetic resonance images. The alendronate group showed pain improvement trends in VAS and WOMAC scores, whereas the control group showed worsening of pain. The alendronate group showed significant improvement in WOMAC pain scores after 12 months (p = 0.031) but no significant prevention of structural osteoarthritis progression, defined as a decrease in JSW >0.30 mm or conversion to total hip arthroplasty. There was significantly larger decrease in the biochemical markers and significantly increased bone density in the alendronate group. Alendronate treatment by standard dose for osteoporosis showed clinical efficacy for decreasing pain but failed to show preventive effects for structural progression of hip osteoarthritis.

Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice

“…Our observations corroborate prior studies showing a decrease in urinary levels of C-terminal telopeptide of type II collagen (CTX-II) and N-terminal telopeptide of type I collagen (NTX-I) with higher dosage of risedronate over time [34,35]. A clinical study by Nishii et al using ALN to treat hip OA in humans also showed a decrease in urinary NTX-I and CTX-II [36]. It is unclear why we did not observe a significant increase in P1NP, even at later time points when there is a strong anabolic response and osteophyte formation.…”

“…However, a 2-year randomized controlled trial of risedronate treatment revealed contradictory results, with no significant improvement of WOMAC score or joint space retention in the knee [38]. Similarly, Nishii et al observed no inhibition of OA progression in patients with treated hip OA after 2 years of ALN treatment [36]. Therefore, in spite of the growing body of clinical work investigating the subject, no definitive conclusion can be reached on the practicality of using bisphosphonates to treat patients with OA.…”

Targeting TGFβ signaling in subchondral bone and articular cartilage homeostasis

“…Though the outcome in human subjects was not as encouraging as in animal OA models 135–139 , specific drugs within the bisphosphonate class did show benefit effects in a few human studies. In the most recent prospective 2-year trial, alendronate treatment successfully improved WOMAC pain score, decrease in biochemical markers in hip osteoarthritis patients 140 . Elderly women being treated with alendronate had a significantly decreased prevalence of knee OA-related subchondral bone lesion and associated with a reduction in knee pain 141 .…”

Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal

“…Likewise trabecular microfractures, which are present in the subchondral bone of early OA articular surfaces [1], are suggested to have a role in OA initiation through localized remodeling and vascular invasion [2]. Moreover, therapeutic studies [3, 4] and investigations into both hydraulic conductance [5] and subchondral-cartilage transport [6] suggest that changes in the subchondral bone plate (SBP) as well as trabecular network are essential to understanding the pathogenesis of OA. Given the complexity and difficulty of measuring early-stage OA cartilage and bone changes in patients or live animals, an appropriate ex vivo cartilage-bone model would be beneficial for further studying the relationships between the properties of both tissues in early disease.…”