Preliminary effects of weekly teriparatide for prevention of knee osteoarthritis progression: a pilot randomized controlled trial

Purpose Subchondral bone fragility contributes to disease progression in knee osteoarthritis (KOA), particularly in osteoporosis. Teriparatide improves subchondral bone quality and shows disease-modifying effects in pre-clinical KOA models, but its clinical efficacy remains unclear. This study assessed the feasibility and variability of teriparatide treatment and explored whether teriparatide may suppress radiographic progression in osteoporotic KOA. Methods This pilot randomized controlled trial (RCT) enrolled women aged ≥60 years with primary osteoporosis and symptomatic KOA. Participants were randomized to weekly teriparatide (56.5 μg subcutaneously) or daily active vitamin D (VD) for 24 months. Co-primary outcomes were changes in joint space width (JSW) and bone trabecular integrity (BTI) on radiographs. Feasibility was assessed by retention, adherence, and adverse events, and variability by measurement deviation and reliability. Analyses followed the intention-to-treat principle. Results Thirteen participants were enrolled (teriparatide, n = 7; VD, n = 6). One participant in each group withdrew within 6 months. One participant in the teriparatide group discontinued after a single dose owing to nausea. Severe adverse events occurred in three patients in the teriparatide group and one in the VD group, none considered related to the intervention. Intra- and inter-rater intraclass correlation coefficients were all >0.9 for the primary outcomes. JSW change at 24 months was smaller in the teriparatide group than in the VD group (−14.8 ± 11.2% vs. −48.0 ± 24.3%). BTI changes were −0.7 ± 16.7% in the teriparatide group and 11.3 ± 8.2% in the VD group. Conclusions This pilot RCT demonstrated acceptable feasibility and variability of teriparatide treatment, and exploratory findings suggested smaller JSW narrowing with teriparatide, providing preliminary data to inform future RCTs.