Nordic Bioscience A/S, Herlev, Herlev, Denmark.
BMC Musculoskelet Disord. 2010 Jun 17;11:125. doi: 10.1186/1471-2474-11-125.
Osteoarthritis (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.
This 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.
At 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.
Bone 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.
Clinical trial registration number (EUDRACT2006-005532-24 & NCT00486369).
骨关节炎（OA）涉及骨和软骨的变化。在某些情况下，这些过程可能会相关联。本研究旨在调查 OA 患者的骨和软骨降解之间的相关性，具体表现为性别、Kellgren-Lawrence（KL）评分、体重指数（BMI）、口服降钙素（sCT）治疗和昼夜变化。
这是一项为期 2 周、双盲、双模拟、随机研究，纳入了 37 名绝经后女性和 36 名男性，年龄 57-75 岁，患有膝关节 OA，KL 评分 I - III。将受试者分为三组：0.6 毫克或 0.8 毫克口服 sCT 或安慰剂，每日两次，共 14 天。研究人员调查了性别、KL 评分或 BMI 与骨吸收标志物血清 I 型胶原 C 端肽（CTX-I）或软骨降解标志物尿 I 型胶原 C 端肽（CTX-II）之间的相关性。
基线时，生物标志物表明，OA 女性的骨和软骨降解水平高于男性。CTX-I 水平明显更高，CTX-II 水平仅略有升高，女性高于男性（p = 0.04 和 p = 0.06）。KL 评分升高与骨吸收无关，但与男女的软骨降解 CTX-II 标志物显著相关（p = 0.007）。BMI 与骨吸收标志物 CTX-I 显著负相关，r = -0.40（p = 0.002），但与 CTX-II 仅呈边缘正相关，r = 0.25（p = 0.12）。在第 1 天和第 14 天治疗的早晨治疗前，sCT 或安慰剂组中均未观察到 CTX-I 和 CTX-II 之间的相关性。然而，口服 sCT 和食物摄入诱导了这些骨和软骨降解标志物之间的明确相关性。在第 1 天和第 14 天的 sCT 剂量治疗的第 4 小时，CTX-I 和 CTX-II 之间的变化显著相关（r = 0.71，p < 0.001）。在安慰剂组中，在第 1 天（r = 0.49，p = 0.02）和第 14 天（r = 0.34，p = 0.06）发现了这两种标志物变化之间的弱显著相关性。
女性的骨吸收水平高于男性，而软骨降解与 KL 评分升高相关，与 BMI 仅呈弱相关。未治疗个体中骨和软骨降解之间无相关性，但口服 sCT 联合或不联合食物治疗以及中午餐可降低骨和软骨降解，并诱导两种标志物之间的相关性。骨和软骨标志物的变化可能有助于确定 OA 的潜在新治疗机会。
临床试验注册号（EUDRACT2006-005532-24 和 NCT00486369）。
