Bone and Joint Research Unit, Service of Rheumatology, IIS Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Osteoarthritis Cartilage. 2011 Oct;19(10):1228-36. doi: 10.1016/j.joca.2011.07.003. Epub 2011 Jul 23.
Impairment of subchondral bone density and quality aggravates cartilage damage in osteoarthritis (OA). Accordingly, we assessed whether improving microstructure and quality at subchondral bone by the bone-forming agent parathyroid hormone (PTH) [1-34] prevent cartilage damage progression in a rabbit model of OA preceded by osteoporosis (OP).
OP was induced in 20 female rabbits. At week 7, these rabbits underwent knee surgery to induce OA and, at week 12, they started either saline vehicle (n=10) or PTH (n=10) for 10 weeks. Ten healthy animals were used as controls. At week 22, microstructure was assessed by micro-computed tomography and bone remodelling by protein expression of alkaline phosphatase (ALP), metalloproteinase-9 (MMP9), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) at subchondral bone. Cartilage damage was evaluated using Mankin score.
PTH reversed the decrease of bone area/tissue area, trabecular thickness, plate thickness, polar moment of inertia, ALP expression and OPG/RANKL ratio, as well as counteracted the increase of fractal dimension and MMP9 expression at subchondral bone of osteoarthritis preceded by osteoporosis (OPOA) rabbits compared to vehicle administration (P<0.05). Likewise, PTH decreased cartilage damage severity in OPOA rabbits. Good correlations were observed between subchondral bone structure or remodelling parameters, and cartilage Mankin score.
Improvement of microstructural and remodelling parameters at subchondral bone by PTH [1-34] contributed to prevent cartilage damage progression in rabbits with early OPOA. These findings support the role of subchondral bone in OA. Further studies are warranted to establish the place of bone-forming agents as potential treatment in OA.
软骨下骨密度和质量的损伤会加重骨关节炎（OA）的软骨损伤。因此，我们评估了骨形成剂甲状旁腺激素（PTH）[1-34]是否通过改善软骨下骨的微结构和质量来预防骨质疏松（OP）前 OA 兔模型中的软骨损伤进展。
20 只雌性兔子诱导 OP。在第 7 周，这些兔子接受膝关节手术以诱导 OA，并且在第 12 周，它们开始接受盐水载体（n=10）或 PTH（n=10）治疗 10 周。10 只健康动物作为对照。在第 22 周，通过微计算机断层扫描评估微结构，通过碱性磷酸酶（ALP）、基质金属蛋白酶 9（MMP9）、骨保护素（OPG）和核因子-κB 配体受体激活剂（RANKL）的蛋白表达评估骨重塑在软骨下骨。使用 Mankin 评分评估软骨损伤。
与载体给药相比，PTH 逆转了骨质疏松症（OPOA）前骨关节炎兔软骨下骨的骨面积/组织面积、小梁厚度、板厚度、极惯性矩、ALP 表达和 OPG/RANKL 比值的降低，并且抵消了 fractal 维度和 MMP9 表达的增加（P<0.05）。同样，PTH 降低了 OPOA 兔子的软骨损伤严重程度。在软骨下骨结构或重塑参数与软骨 Mankin 评分之间观察到良好的相关性。
PTH[1-34]改善软骨下骨的微结构和重塑参数有助于预防早期 OPOA 兔的软骨损伤进展。这些发现支持软骨下骨在 OA 中的作用。需要进一步的研究来确定骨形成剂作为 OA 潜在治疗方法的地位。
