Bettica Paolo, Cline Gary, Hart Deborah J, Meyer Joan, Spector Tim D
Procter & Gamble Pharmaceuticals, Staines, UK.
Arthritis Rheum. 2002 Dec;46(12):3178-84. doi: 10.1002/art.10630.
Several studies have suggested that increased subchondral bone turnover is a determinant of progression of osteoarthritis (OA). To test this hypothesis, the level of urinary N-terminal type I collagen telopeptides (NTx) and C-terminal type I collagen telopeptides (CTx), which are validated markers of bone resorption, was measured at 3 different time points in a subset of patients from the Chingford study.
The original Chingford study population comprised 1,003 women. From this group, postmenopausal women not receiving any bone-modifying medication who had a baseline knee radiograph and a repeat radiograph 4 years later, and for whom a baseline lumbar spine bone mineral density (BMD) measurement was available, were identified and separated into 4 groups as follows: controls (n = 50), progressive OA (n = 71), nonprogressive OA (n = 36), and osteoporosis (n = 59). NTx and CTx were measured in urine samples collected at baseline, year 1, and year 2.
Patient age and years since menopause were similar among groups at baseline. As expected, both body mass index (BMI) and BMD were lowest in patients with osteoporosis. Median resorption marker levels over the 3 time points were 31-87% higher in patients with either progressive OA or osteoporosis than in controls and patients with nonprogressive OA (P < 0.01, except for levels of CTx in patients with progressive OA versus nonprogressive OA). Levels of NTx and CTx did not differ significantly between women with progressive OA (defined either by the presence of osteophytes or by joint space narrowing) and those with osteoporosis or between controls and women with nonprogressive OA. Results were essentially unchanged after adjustment for age, BMI, BMD, and past use of hormone replacement therapy, or when NTx and CTx values at each time point were analyzed separately.
Our data demonstrate that bone resorption is increased in patients with progressive knee OA and is not increased in those with nonprogressive knee OA. The increase in bone resorption seen in patients with progressive knee OA is similar to that observed in patients with osteoporosis. Altered bone turnover may be a diagnostic or therapeutic target in patients with progressive OA.
多项研究表明,软骨下骨转换增加是骨关节炎(OA)进展的一个决定因素。为验证这一假设,在来自Chingford研究的部分患者中,于3个不同时间点测量了尿I型胶原N端肽(NTx)和I型胶原C端肽(CTx)水平,这两种物质是经过验证的骨吸收标志物。
Chingford研究的原始人群包括1003名女性。从该组中,识别出未接受任何骨改良药物治疗、有基线膝关节X线片且4年后有重复X线片、并且有基线腰椎骨密度(BMD)测量值的绝经后女性,并将其分为以下4组:对照组(n = 50)、进展性OA组(n = 71)、非进展性OA组(n = 36)和骨质疏松组(n = 59)。在基线、第1年和第2年收集的尿液样本中测量NTx和CTx。
各组患者在基线时的年龄和绝经年限相似。正如预期的那样,骨质疏松患者的体重指数(BMI)和骨密度均最低。进展性OA患者或骨质疏松患者在3个时间点的中位吸收标志物水平比对照组和非进展性OA患者高31 - 87%(进展性OA患者与非进展性OA患者的CTx水平除外,P < 0.01)。进展性OA女性(根据骨赘的存在或关节间隙狭窄定义)与骨质疏松女性之间,以及对照组与非进展性OA女性之间,NTx和CTx水平无显著差异。在对年龄、BMI、骨密度和既往激素替代疗法使用情况进行调整后,或者在分别分析每个时间点的NTx和CTx值时,结果基本不变。
我们的数据表明,进展性膝关节OA患者的骨吸收增加,而非进展性膝关节OA患者的骨吸收未增加。进展性膝关节OA患者中观察到的骨吸收增加与骨质疏松患者中观察到的相似。骨转换改变可能是进展性OA患者的一个诊断或治疗靶点。