Abstract
BackgroundOsteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass Index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation.MethodsThis study was a 2-week, double-blind, double-dummy, randomized study including 37 postmenopausal women and 36 men, aged 57-75 years, with painful knee OA, and a KL-score of I - III. Subjects were allocated to one of three treatment arms: 0.6 mg or 0.8 mg oral sCT, or placebo given twice-daily for 14 days. Correlations between gender, KL score, or BMI and the bone resorption marker, serum C-terminal telopeptide of collagen type I (CTX-I), or the cartilage degradation marker, urine C-terminal telopeptide of collagen type II (CTX-II) were investigated.ResultsAt baseline, biomarkers indicated women with OA experienced higher bone and cartilage degradation than men. CTX-I levels were significantly higher, and CTX-II levels only marginally higher, in women than in men (p = 0.04 and p = 0.06, respectively). Increasing KL score was not correlated with bone resorption, but was significantly associated with the cartilage degradation CTX-II marker in both men and women (p = 0.007). BMI was significantly and negatively correlated to the bone resorption marker CTX-I, r = -0.40 (p = 0.002), but showed only a borderline positive correlation to CTX-II, r = 0.25 (p = 0.12). Before morning treatments on days 1 and 14, no correlation was seen between CTX-I and CTX-II in either the sCT or placebo group. However, oral sCT and food intake induced a clear correlation between these bone and cartilage degradation markers. Four hours after the first sCT dose on treatment days 1 and 14, a significant correlation (r = 0.71, p < 0.001) between changes in both CTX-I and CTX-II was seen. In the placebo group a weakly significant correlation between changes in both markers was found on day 1 (r = 0.49, p = 0.02), but not on day 14.ConclusionBone resorption was higher in females than males, while cartilage degradation was correlated with increasing KL-score and only weakly associated with BMI. Bone and cartilage degradation were not correlated in untreated individuals, but dosing with oral sCT with or without food, and a mid-day meal, decreased bone and cartilage degradation and induced a correlation between both markers. Changes in bone and cartilage markers may aid in the identification of potential new treatment opportunities for OA.Trial RegistrationClinical trial registration number (EUDRACT2006-005532-24 & NCT00486369)
Highlights
Osteoarthritis (OA) involves changes in both bone and cartilage
Baseline measurements of C-terminal telopeptide of collagen type I (CTX-I) and C-terminal telopeptide of collagen type I (CTX-II) showed no significant differences between the treatment groups (Table 2)
A trend towards an increase in CTX-I with increasing OA severity was seen in women, it was completely absent in men
Summary
Osteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. An increasing line of evidence suggests that there are strong inter-relationships between the subchondral bone and the articular cartilage [1] At present it is neither well-documented nor understood which parameters are initiators or drivers of the disease. Among the other known risk factors of OA are increasing age, sex, significant trauma, obesity and the resulting excessive loading, altered gait and altered biomechanics (e.g. varus or valgus deformity) [9,10,11,12,13,14,15,16,17] This long list of risk factors for the initiation and progression of OA and physiological mechanisms affecting both bone and cartilage turnover are currently under investigation by several independent research groups using different approaches and technologies
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