A noninvasive, in vivo model for studying strain adaptive bone modeling

We present a noninvasive, in vivo model for strain application in the tibiae of rats. The hind limb of each animal was placed into a device that applied four point bending to the tibia. Bending was applied in the medial-lateral direction causing compression on the lateral surface of the tibia and tension on the anteromedial surface. The peak strain magnitudes were estimated to be between 1600 and 3500 mu strain. In this pilot work, data were collected from 12 rats. The rats received either one cycle per day, four cycles per day, 12 cycles per day, 36 cycles per day, or 108 cycles per day of bending. The experimental (right) tibiae from all of the rats showed new bone formation after 12 days. The control (left) tibiae showed no new bone formation over this period. A better organized, dense bony reaction occurred in regions of lesser strains than in regions of higher strains, where there was a large accumulation of bone easily identified as woven. The organization and density of the newly formed bone appeared to be inversely related to the peak strains in the region. After 40 days of daily loading, the new bone area appeared to be more compact and better mineralized. However, bone formation was still occurring after 40 days. The results of this study suggest that woven bone formation occurred due to the bending stimulus and not due to pathology.     

Histomorphometric effects of calcium or calcium plus 25-hydroxyvitamin D3 therapy in senile osteoporosis

To evaluate the effects of calcium and 25-OHD in the therapy of senile osteoporosis, we studied a group of 39 women aged 69 +/- 7 (standard deviation, SD) years with severe osteoporosis. The group was characterized histomorphometrically by depressed bone remodeling rates without hyperosteoidosis. No subject had risk factors for osteopenia other than their age and postmenopausal status, and no subject was receiving therapy for bone disease at the onset of the study. Subjects were followed for 2 years after randomization to receive either 1200 mg/day of calcium (as calcium carbonate) and 40 micrograms/day of 25-OHD (calcium-25-OHD group), or 1200 mg/day of calcium plus placebo (calcium-placebo group). Calcium-25-OHD resulted in a clear increase in 25-OHD levels (p less than 0.001) and an increase in calcium absorption as indicated by urinary calcium excretion. Nevertheless, there was no significant change in fasting serum calcium, phosphorus, alkaline phosphatase, PTH, or 1,25-(OH)2D in either group. Radial and phalangeal bone mineral content and trabecular bone volume in the biopsied patients remained stable in both groups over the 2 year period. Unexpectedly, repeat bone biopsies revealed a clear improvement in the rate of mineralization in both groups, presumably as a result of the calcium supplementation alone. In summary, calcium-placebo and calcium-25-OHD treatment were both associated with stable appendicular bone mineral content in women with senile osteopenia. The finding of an effect of calcium supplementation on the rate of mineralization indicates that relative calcium deficiency may impair the mineralization phase of remodeling.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.     

Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis.

A genome-wide screen was conducted using a large white sample to identify QTLs for FNCS geometry. We found significant linkage of FNCS parameters to 20q12 and Xq25, plus significant epistatic interactions and sex-specific QTLs influencing FNCS geometry variation. INTRODUCTION: Bone geometry, a highly heritable trait, is a critical component of bone strength that significantly determines osteoporotic fracture risk. Specifically, femoral neck cross-sectional (FNCS) geometry is significantly associated with hip fracture risk as well as genetic factors. However, genetic research in this respect is still in its infancy. MATERIALS AND METHODS: To identify the underlying genomic regions influencing FNCS variables, we performed a remarkably large-scale whole genome linkage scan involving 3998 individuals from 434 pedigrees for four FNCS geometry parameters, namely buckling ratio (BR), cross-sectional area (CSA), cortical thickness (CT), and section modulus (Z). The major statistical approach adopted is the variance component method implemented in SOLAR. RESULTS: Significant linkage evidence (threshold LOD = 3.72 after correction for tests of multiple phenotypes) was found in the regions of 20q12 and Xq25 for CT (LOD = 4.28 and 3.90, respectively). We also identified eight suggestive linkage signals (threshold LOD = 2.31 after correction for multiple tests) for the respective geometry traits. The above findings were supported by principal component linkage analysis. Of them, 20q12 was of particular interest because it was linked to multiple FNCS geometry traits and significantly interacted with five other genomic loci to influence CSA variation. The effects of 20q12 on FNCS geometry were present in both male and female subgroups. Subgroup analysis also revealed the presence of sex-specific quantitative trait loci (QTLs) for FNCS traits in the regions such as 2p14, 3q26, 7q21 and 15q21. CONCLUSIONS: Our findings laid a foundation for further replication and fine-mapping studies as well as for positional and functional candidate gene studies, aiming at eventually finding the causal genetic variants and hidden mechanisms concerning FNCS geometry variation and the associated hip fractures.     

Complex segregation analyses of bone mineral density in Chinese

China has the largest population in the world; approximately 7% of the total population suffers from primary osteoporosis. Osteoporosis is mainly characterized by low bone mineral density (BMD). In the present study, familial correlation and segregation analyses for spine and hip BMDs have been undertaken for the first time in a Chinese sample composed of 401 nuclear families with a total of 1,260 individuals. The results indicate a major gene of additive inheritance for hip BMD, whereas there is no evidence of a major gene influencing spine BMD. Significant familial residual effects are found for both traits, and heritability estimates (±SE) for spine and hip BMDs are 0.807(0.099) and 0.897(0.101), respectively. Sex and age differences in genotype‐specific average BMD are also observed. This study provides the first evidence quantifying the high degree of genetic determination of BMD variation in the Chinese.     

Accuracy of magnetic resonance imaging compared to computerized tomography and renal selective angiography in preoperatively staging renal cell carcinoma.

During 1986 and 1987, 47 patients with renal cell carcinoma were evaluated preoperatively with CT, angiography and MRI. The preoperative tumor stage (T), lymph node metastases and venous involvement determined with the three methods were compared to the operative and histopathological findings. For T stage, angiography proved less accurate (54%) than CT (64%) or MRI (63%). MRI was found to be superior to CT in assessing lymph nodes, with an overall accuracy of 89% and sensitivity of 100% compared to 77 and 60%, respectively, of CT. For venous involvement CT was overall more accurate (74%) than angiography (65%) or MRI (63%). All three methods expressed a low sensitivity (between 31 and 41%) and a high specificity (between 95 and 100%) for detecting venous involvement. The minimal advantages of MRI compared to its high cost do not justify its routine use. CT remains the method of choice in staging preoperatively renal cell carcinoma.     

Evidence for a major gene underlying bone size variation in the Chinese

Osteoporosis is a major public health problem defined as a loss of bone strength, of which bone size is an important determinant. In the present study, familial correlation and segregation analyses for the spine and hip bone sizes were performed for the first time in a Chinese sample composed of 393 nuclear families with a total of 1,193 individuals. The results indicate a major gene of codominant inheritance for spine bone size; however, there is no evidence of a major gene influencing hip bone size. Significant familial residual effects are found for both traits, suggesting their polygenic inheritance. Heritability estimates (±SE) for spine and hip bone size were 0.62 (0.13) and 0.59 (0.12), respectively. Sex and age differences in genotype‐specific average bone size were observed. Compared with our previous study on bone mineral density (BMD) in the same population, this study suggests that genetic determination of bone size may be different from that of BMD, and thus studying bone size as one surrogate phenotype for osteoporotic fractures may be necessary. Am. J. Hum. Biol. 16:68–77, 2004. © 2003 Wiley‐Liss, Inc.