A chemometric analysis for evaluation of early-stage cartilage degradation by infrared fiber-optic probe spectroscopy.

In vivo identification of early-stage cartilage degradation could positively impact disease progression in osteoarthritis, but to date remains a challenge. The primary goal of this study was to develop an infrared fiber-optic probe (IFOP) chemometric method using partial least squares (PLS1) to objectively determine the degree of cartilage degradation. Arthritic human tibial plateaus (N = 61) were obtained during knee replacement surgery and analyzed by IFOP. IFOP data were collected from multiple regions of each specimen and the cartilage graded according to the Collins Visual Grading Scale of 0, 1, 2, or 3. These grades correspond to cartilage morphology that displayed normal, swelling or softening, superficially slight fibrillation, and deeper fibrillation or serious fibrillation, respectively. The model focused on detecting early cartilage degradation and therefore utilized data from grades 0, 1, and 2. The best PLS1 calibration utilized the spectral range 1733-984 cm(-1), and independent validation of the model utilizing 206 spectra to create a model and 105 independent test spectra resulted in a correlation between the predicted and actual Collins grade of R2 = 0.8228 with a standard error of prediction of 0.258 with a PLS1 rank of 15 PLS factors. A preliminary PLS1 calibration that utilized a cross-validation technique to investigate the possibility of correlation with histological tissue grade (33 spectra from 18 tissues) resulted in R2 = 0.8408 using only eight PLS factors, a very encouraging outcome. Thus, the groundwork for use of IFOP-based chemometric determination of early cartilage degradation has been established.

Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model.

Recent non-placebo-controlled studies of the bisphosphonate pamidronate have shown it to be effective in reducing fractures and improving bone density in infants and children with osteogenesis imperfecta (OI). To evaluate the effects of bisphosphonate treatment in a controlled study, the oim/oim mouse model of OI was studied. Nursing infant mouse pups (approximately 2 wk old) with moderate to severe OI (oim/oim mouse) and age- and background-matched control mice (+/+) were treated either with the third-generation bisphosphonate alendronate (ALN), or with saline. Fracture risk, bone quality, and growth were evaluated over a 12-wk treatment period. ALN at a dose of 0.03 mg/kg/d or saline was administered via s.c. injection to infant oim/oim and wild-type (+/+) mice from 2 to 14 wk of age (n = 20 per subgroup). The average number of fractures sustained by the ALN-treated oim/oim mice was reduced significantly compared with the untreated oim/oim mice (0.7 +/- 0.7 fractures/mouse versus 2.0 +/- 0.2 fractures/mouse). Bone density increased significantly in the femur and the spine with treatment (2.0 +/- 0.5 versus 1.2 +/- 0.5 in femur and 2.1 +/- 0.5 versus1.6 +/- 0.5 in spine). Histologic evaluation revealed the percentage of metaphyseal tibial bone increased significantly with treatment in both +/+ and oim/oim mice. Mechanical testing revealed an increase in structural stiffness for both treated +/+ and oim/oim mice compared with untreated animals. None of the material properties examined were significantly altered with treatment, nor was spinal curvature affected. Weight gain and long bone growth were comparable in the treated and untreated oim/oim mice. In wild-type mice, femur lengths were significantly shorter in the treated mice compared with untreated counterparts. This animal study demonstrates that treatment of OI in mice as early as 2 wk of age with ALN appears to be effective in reducing fractures and increasing bone properties. Based on the data from this study, ALN therapy in infants with OI should prove to be effective.