Evaluation of modal damping factor as a diagnostic tool for osteoporosis and its relation with serum osteocalcin and collagen I N-telopeptide for monitoring the efficacy of alendronate in ovariectomized rats.J Pharm Biomed Anal 2006; 41(3):891-7JP
Osteoporosis is a metabolic bone disease characterized by reduced bone mass and deterioration of bone microarchitecture. It results from the shift of the osteoblast-osteoclast activity equilibrium in favor of the later. Although, a number of biochemical markers, such as collagen I N-telopeptide (NTx) and osteocalcin (OC), have been used for monitoring bone remodeling, a new, monitoring, non-invasive method, which is based on the measurement of the dynamic characteristic of bone and is known as modal damping factor (MDF), has not been evaluated as a diagnostic tool for osteoporosis. Bisphosphonates, such as alendronate, have an established role in the treatment of osteoporosis. The aim of the present study was, therefore, to evaluate the effects of alendronate on the levels of MDF, serum NTx and OC on osteoporosis induced by ovariectomy in rats. Furthermore, the effects of alendronate on osteoporosis have been histologically evaluated. Fifteen adult female Wistar rats were bilaterally ovariectomized and osteoporosis was histologically confirmed and by the use of peripheral quantitative computerized tomography (pQCT). MDF was applied to assess the bone structural integrity. The serum levels of NTx (37.4+/-0.5 nM bone collagen equivalents, BCE) and OC (111.0+/-8.2 ng/mL) were found to significantly increase following ovariectomy (72.0+/-2.9 nM BCE and 213.5+/-12.1 ng/mL, respectively, p<0.001). As assessed by histology and the levels of NTx and OC in sera, animals treated with alendronate presented a statistically significant deceleration in the progression of the disease in comparison to the no-therapy control group (alendronate group NTx levels: 146.3+/-8.9 nM BCE versus no-therapy control group NTx levels: 265.3+/-14.0 nM BCE, p<0.001, alendronate group OC levels: 205.6+/-18.2 ng/mL versus no-therapy group OC levels: 353.9+/-26.1 ng/mL, p<0.001). Data obtained from the vibration analysis performed illustrated that the change in damping was equal or greater to the change in total and trabecular density, respectively. Damping increased with decreasing bone density, as expected, given that damping accounts for the structural integrity of bone (MDF value before ovariectomy: 0.058+/-0.003 versus MDF value after ovariectomy: 0.098+/-0.003, p<0.001). The higher damping values correspond to more deteriorated structures. In particular, both total and trabecular density were significantly decreased following ovariectomy (total density before ovariectomy: 702.4+/-19.0 versus total density after ovariectomy: 542.2+/-12.8, p<0.001, trabecular density before ovariectomy: 445.3+/-13.0 versus trabecular density after ovariectomy: 396.7+/-8.4, p<0.05). MDF value of the alendronate group (0.07+/-0.002) was significantly lower (p<0.001) as compared to MDF value after ovariectomy (0.098+/-0.003) and that of the no-therapy group (0.1+/-0.004, p<0.001). The administration of alendronate seemed to have no effect on either total or trabecular density, since both parameters continued to decrease (alendronate group total density: 549.4+/-12.3, alendronate group trabecular density: 368.4+/-14.7). However, when this was compared to the no-therapy group, a statistically significant difference of total density at the 0.05 level was observed (no-therapy total density: 464.8+/-9.1). The results of this study suggest that combined measurements of MDF, NTx and OC may be a potential diagnostic tool for osteoporosis and monitoring bone integrity during treatment with bisphosphonates. Furthermore, administration of alendronate showed to offer a critical deceleration in the progression of osteoporosis.