The effect of androstenedione/estrone supplementation on cortical and cancellous bone in the young intact female monkey: a model for the effects of polycystic ovarian disease on the skeleton?

The goal of this study was to determine the effects of chronically elevated blood androstenedione and estrone levels on the quality and quantity of both cancellous (trabecular) and cortical bone in a young (mean age 9.4 years) female primate model (M. fascicularis). Thirteen intact female monkeys received continuous androstenedione/estrone supplementation via subcutaneous implants over a 24-month period to simulate the human condition known as polycystic ovarian disease (PCOD). A group of 16 untreated intact age-matched female monkeys served as controls. Lumbar spine and whole body bone mineral density (BMD) status was determined mid-study by dual photon absorptiometry (DPA); subsequent analysis of the bone related to data obtained following the 2-year treatment period without further BMD measurement. Bone markers, including serum acid phosphatase, total bone alkaline phosphatase, bone gla protein and tartrate-resistant acid phosphatase were measured at the end of the study. At necropsy, the lumbar vertebrae and femora were recovered in order to analyze the bone mineral quality and quantity of cancellous and cortical bone respectively and to compare these with the control group. Mineralization profiles of the vertebrae and femora were obtained using the density fractionation technique. Chemical analysis of the three largest fractions retrieved by density fractionation was performed to evaluate differences in %Ca, %P, Ca/P ratio and mineral content (%Ca + %PO4) between control and experimental groups. In addition, unfractionated bone powder was examined by X-ray diffraction to identify any changes in crystal size. Coronal sections of vertebrae were analyzed for structural parameters using histomorphometry and image analysis. Cross-sections taken at the midshaft diaphyseal femora were analyzed for structural macroscopic and intracortical parameters. There was a significant increase in BMD at the L2-L4 region in the treatment group compared with the control groups (p < 0.005) as measured at 1 year into the trial. Serum acid phosphatase was significantly lower (p < 0.05) in the treatment group compared with the controls near study termination. A nonsignificant shift in the mineralization profile of the vertebrae towards less dense bone was observed in the treatment group, while there was a significant shift in the mineralization profile towards more dense bone in the treated femora compared with controls (p < 0.05) after a 2-year period. There was no difference between treatment and control groups in terms of size/strain of the cortical or cancellous bone crystal as detected by X-ray diffraction. There was a significant increase in cancellous bone area (B.Ar.) (p < 0.02) and a significant increase (p < 0.05) in mean trabecular width with a corresponding decrease in trabecular separation (p < 0.03) in the experimental group compared with the controls. There were no significant changes in osteoid parameters (perimeter, area or width) or eroded perimeter measurements in the experimental group compared with the controls. In the experimental group, trabecular strut analysis showed a significant increase in the number of nodes (p < 0.02) and in the total strut length (p < 0.003) compared with the controls. There was also a significant increase in the node to node (p < 0.04) and node to terminus (p < 0.004) strut length in the treatment group compared with the controls. A significant increase in B.Ar. without concurrent indices of ongoing remodelling differing from controls suggests that cancellous bone of the vertebral body in the treated young female primate had been receptive to the anabolic stimulus of androstenedione/estrone supplementation over the 2-year period. In contrast, macroscopic parameters of cortical bone such as perimeter, area and width were preserved over the 2-year course, while intracortical remodeling was evident with increased percent porosity (p < 0.001), osteonal bone (p < 0.01) and osteonal density (p < 0.01) observed in the treatment group compared with the controls. The endocrine profile of both elevated androstenedione and estrone levels in an intact female primate of reproductive age may identify differential effects of the condition known as polycystic ovarian disease on the skeletal compartments.

Interrater and intrarater reliability in the measurement of kyphosis in postmenopausal women with osteoporosis.

STUDY DESIGN: A reliability study was performed using repeated random measurements involving three observers, 26 subjects and three instruments. OBJECTIVES: To determine the most reliable, cost-effective, noninvasive, and clinically feasible method of measuring spinal kyphosis. SUMMARY OF BACKGROUND DATA: The most clinically useful, noninvasive and reliable method of measuring postural deformity in spinal osteoporosis (kyphosis) remains unqualified. Despite traditional use of costly, invasive roentgenographs for the evaluation of spinal kyphosis, the reliability of this method remains questionable. METHODS: Twenty-six postmenopausal women with known bone mineral density and a diagnosis of osteoporosis were recruited from the Osteoporosis Program at Women's College Hospital, Toronto, Canada. Non-invasive measurements of thoracic kyphosis were obtained by three trained examiners using the DeBrunner's kyphometer and the flexicurve ruler. The intrarater and interrater reliability of and between each method was compared, using roentgenographic films obtained in the sagittal plane. Spinal posture was classified according to the method of Itoi (1990). Statistical computations were performed using SAS statistical software. RESULTS: Consistent measurements were obtained with the DeBrunner's kyphometer and the flexicurve ruler by each observer, according to the results of critical two-way analysis of variance (Intraclass Correlation Coefficient 2, 1). Measurements in two subgroups, healthy backs (n = 11) and rounded backs (n = 13), showed consistent use of each noninvasive instrument with some examiner preference for specific tools. There was marginally better intrarater and interrater reliability using the DeBrunner's kyphometer compared with that obtained with the flexicurve ruler. Two-way analysis of variance (Intraclass Correlation Coefficient 2, 1) of collapsed data showed no significant difference in the reliability of the kyphometer, flexicurve ruler, or roentgenographs in the measurement of thoracic kyphosis. CONCLUSIONS: The flexicurve ruler and DeBrunner's kyphometer had the closest agreement in the measurement of spinal kyphosis. The kyphometer demonstrated the least variation in intrarater and interrater reliability when compared with the flexicurve ruler and roentgenographs. The flexicurve ruler permits qualitative assessment of posture, however, and is the most cost-effective instrument. The results of this study challenge the traditional belief that roentgenographic analysis is the best method for evaluating spinal kyphosis. The DeBrunner's kyphometer and flexible ruler may represent viable, cost-effective and noninvasive alternatives to roentgenographic evaluation of spinal kyphosis.