Autologous bone harvested from the iliac crest is a commonly used grafting material for a number of surgical procedures; however, there is documented morbidity associated with secondary site harvesting. Because demineralized bone matrix (DBM) is inherently osteoinductive (i.e., it facilitates differentiation of uncommitted connective tissue cells into bone-forming cells), it has potential appeal as a bone-graft substitute. Allogeneic DBM usage has intrinsic shortcomings related to procuring, processing and characterizing bone from a human donor pool. Xenogeneic bone represents an unlimited supply of available material if it can be processed to render it safe for transplantation to the human host. It is hypothesized that reported immunogenicity and non-viability of xenogeneic DBM results from lipids and plasma proteins not removed during typical demineralization processes. The authors propose a rigorous examination of this hypothesis, followed by several pivotal studies to determine the effectiveness of xenogeneic DBM.

Animals↗

PubMed1993

Menopause without symptoms: the endocrinology of menopause among rural Mayan Indians.

OBJECTIVE: Our purpose was to determine the characteristics of menopause among Mayan women who did not have menopausal symptoms. STUDY DESIGN: A cross-sectional study of Mayan women from Chichimila, Mexico, was performed. Demographic information, history and physical examination, hormone concentrations, and radial bone density measurement were obtained. RESULTS: Fifty-two postmenopausal women were compared with 26 premenopausal women. Menopause occurred at 44.3 +/- 4.4 years. None of the women admitted to hot flushes and did not recall significant menopausal symptoms. Hormone levels included elevated follicle-stimulating hormone (66.6 +/- 29 mlU/ml), low estradiol and estrone (9.4 +/- 8.3 and 13.3 +/- 7.8 pg/ml), estrone greater than estradiol levels, normal levels of testosterone and androstenedione (0.17 +/- 0.14 and 0.31 +/- 0.17 ng/ml). Bone mineral density declined with age, but height did not. Clinical evidence of osteoporosis was not detected. CONCLUSIONS: Lack of symptoms during the menopausal transition is not attributable to a difference in endocrinology. Postmenopausal Mayan women are estrogen deprived and experience age-related bone demineralization but do not have a high incidence of osteoporotic fractures.

Adult↗

PubMed1991

Skeletal integrity in premenopausal and postmenopausal women receiving long-term L-thyroxine therapy.

PURPOSE: The impact of long-term L-thyroxine replacement therapy on skeletal integrity is a growing concern because of the large number of women receiving thyroid hormone therapy. The purpose of this study was to examine the hypothesis that long-term L-thyroxine therapy in which the free thyroxine index (FT4I) is maintained within a physiologic range has minimal impact on vertebral or femoral bone mineral density in both premenopausal and postmenopausal women. PATIENTS AND METHODS: We measured hip integral and spinal trabecular and integral bone densities in 28 premenopausal and 28 postmenopausal women who had been receiving L-thyroxine therapy for a median of 12 and 15 years, respectively, and in whom therapy was titrated to keep the FT4I within the normal range. The relationship between bone density parameters and thyroid hormone status was examined using univariate and multivariate statistical methods. RESULTS: Seventy-nine percent of the premenopausal women and 86% of the postmenopausal women had FT4I values in the normal range at the time of bone density determination. Moreover, throughout the study's duration, the majority of annually measured values were in the normal range for more than 80% of subjects. Premenopausal women had slightly lower bone density than would be expected for age: -6.7% (z = -0.39 +/- 0.74 [mean +/- SD], p less than 0.01), -3.1% (z = -0.22 +/- 0.78, p = 0.15), and -5.1% (z = -0.36 +/- 0.74, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. Postmenopausal women likewise had slightly lower bone density values that were significant only at the hip: -0.2% (z = -0.01 +/- 1.01, p = 0.95), -1.0% (z = -0.05 +/- 1.11, p = 0.80), and -6.2% (z = -0.39 +/- 0.80, p less than 0.02) for spinal trabecular, spinal integral, and hip integral bone density, respectively. When patients with previously treated Graves' disease (n = 4 in each group) were eliminated, the differences in bone density at the hip were no longer seen. Correlation analysis revealed only weak and generally nonsignificant relationships between parameters of thyroid hormone status and bone density at any site in either subgroup. Results of multiple regression analysis among the pooled data of all subjects showed that age provided a consistently significant contribution (R2 = 0.18 to 0.66) to the variability in bone density at the spine and the hip, but parameters of thyroid hormone status did not. CONCLUSION: These data provide the first supportive evidence that long-term L-thyroxine therapy that maintains the FT4I in the physiologic range is associated with a statistically significant, but clinically minimal, decrement in spinal and hip bone density in both premenopausal and postmenopausal women. The decrement at the hip was entirely due to the inclusion of patients with treated Graves' diseases. Thus, the changes in bone density in women receiving long-term L-thyroxine therapy are minimal at most and should not be a contraindication to therapy.

Adult↗

PubMed1990

Spinal bone mineral density measured with quantitative CT: effect of region of interest, vertebral level, and technique.

This study documents the relationship between different vertebral bone compartments with quantitative computed tomography (CT). Four distinct patient groups were investigated: healthy pre- and early postmenopausal women as well as healthy and osteoporotic late postmenopausal women. Three different regions of interest (ROIs) were employed: the elliptical ROI located in the anterior trabecular portion of the vertebral body, the peeled ROI of irregular shape that circumscribes most of the trabecular bone, and the integral ROI including all bone except for the transverse processes. Both single- and dual-energy quantitative CT techniques were employed at T-12 through L-3. Correlation between measurements in the elliptical and peeled ROIs was high (r = .985). The authors concluded that either ROI is acceptable for clinical use. The decrements in bone mineral density (BMD) for the integral ROI were smaller than those for the elliptical ROI. Dual-energy measurements were consistently higher than single-energy measurements. BMD as a function of vertebral level decreased systematically from T-12 to L-3. However, the average density of T-12 through L-3 can be accurately predicted by the average density of L-1 and L-2 (r = .997). Precision did not deteriorate significantly when BMD was expressed as the average of L-1 and L-2 (1.5%) instead of T-12 through L-3 (1.4%). In this study the data suggest a modified quantitative CT protocol for clinical applications in which BMD of only L-1 and L-2 are measured at a fixed gantry tilt.

Adult↗

PubMed1989

Models of spinal trabecular bone loss as determined by quantitative computed tomography.

Noninvasive bone densitometry techniques have significantly improved our understanding of the pattern and magnitude of bone loss over the life span. Quantitative computed tomography (QCT) is capable of selectively measuring highly labile trabecular bone in the central portion of the vertebrae. Trabecular bone mineral density (mg/ml) was determined in 538 healthy women ranging in age from 20 to 80 using GE CT/T scanners at 80 kVp. Various statistical regressions were performed for the entire population to describe the general pattern of bone loss from the spine; a cubic model (r = -0.69, SEE = 26.0 mg/ml) was found to be statistically superior (p less than 0.01) to linear, quadratic, or exponential models. An average bone loss was approximated from these regression analyses with a yearly absolute rate of -2.02 +/- 0.097 mg/ml per year (p less than 0.0001). The average rate of change for premenopausal women was -0.45 mg/ml per year (p less than 0.05), for perimenopausal women was -4.39 mg/ml per year (p less than 0.0001) and for postmenopausal women was -1.99 mg/ml per year (p less than 0.0001). QCT values were also stratified into 5 and 10 year age groups and analyzed separately for pre- and postmenopausal women. The 5 and 10 year interval stratification revealed no identifiable bone density decrements prior to midlife using analysis of variance statistical methods; significant losses of bone mineral density were noted to correspond with the usual time of menopause and to continue into old age. Various two-phase regressions were employed using age and menstrual status to improve the description of age- and menopause-related bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Familial hypophosphatemic rickets: bone mass measurements in children following therapy with calcitriol and supplemental phosphate.

Familial hypophosphatemic rickets is characterized by defective skeletal mineralization resulting in abnormal growth and development. The pathologic and radiologic correlates of this syndrome have been given some investigation, but the effect of this mineralization defect on bone mineral density has not been adequately assessed. We measured axial and appendicular bone mineral in 17 children (mean age 5.59 +/- 4.87) with familial hypophosphatemia at baseline and at 6-month intervals after initiation of therapy with vitamin D3 (calcitriol) and phosphate supplementation. Noninvasive quantitative techniques included single photon absorptiometry (SPA) of the radius, combined cortical thickness (CCT) of the second metacarpal, and quantitative computed tomography (QCT) of vertebral trabecular bone. Thoraco-lumbar and hand/wrist radiographs were qualitatively assessed for the prevalence and severity of osteosclerosis, rickets, and other parameters indicative of metabolic bone disease as well as skeletal age. Quantitative determinations of bone mineral by each technique were compared with normal values for age and sex, and individual standardized scores (z-scores) were calculated at each measurement interval. Standard scores were also calculated for bone age-adjusted mineral values. At baseline, spinal trabecular bone by QCT was not significantly different from normal values; however, measurements of peripheral cortical bone by either SPA or CCT were significantly lower than values for normal children of the same age and sex (P = 0.05 and P = 0.01, respectively). Following therapy with calcitriol and phosphate, peripheral bone mass was not shown to improve significantly when contiguous standard scores were compared even when values were adjusted for bone age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Preventing osteoporosis with exercise: a review with emphasis on methodology.

Exercise is thought to have considerable potential as a preventive for osteoporosis. We critically examined 27 studies that address the prophylactic role of exercise in osteoporosis. The results from both cross-sectional and longitudinal studies showed that differences in bone mass were more pronounced in the axial skeleton as opposed to the peripheral compact skeleton. The 17 cross-sectional studies demonstrated greater bone mass among highly trained athletes compared with sedentary subjects, while results among recreational athletes were inconsistent. The 10 prospective investigations examining the effect of exercise on bone mass yielded conflicting results; only one study of six found an overall positive response in compact bone mass at the radial site, and only one study examining the spine showed a significant gain among the exercisers. Additionally, all the prospective investigations included serious methodologic flaws; most failed to employ a randomized design, appropriate estimates of sample size were lacking, none provided information on blind outcome assessment, and most studies were of short duration. Current evidence suggests that exercise may have only limited value in affecting bone mass in the short term and widespread recommendations for the prophylactic use of exercise should await further validation using better methodological rigor.

Bone and Bones↗

PubMed1989

Appropriate use of bone densitometry.

The authors discuss current capabilities of three common bone densitometry techniques--single photon absorptiometry, dual photon absorptiometry, and quantitative computed tomography--and potential capabilities of new innovations of each of these techniques. They believe that use of bone densitometry is valid in the following four clinical applications and recommend its usage to (a) assess patients with metabolic diseases known to affect the skeleton, (b) assess perimenopausal women for initiation of estrogen replacement therapy, (c) establish a diagnosis of osteoporosis or assess its severity in the context of general clinical care, and (d) monitor the efficacy of treatment interventions or the natural course of disease.

Bone Diseases, Metabolic↗

PubMed1989

Determinants of bone density among athletes engaged in weight-bearing and non-weight-bearing activity.

To identify the factors associated with greater bone density among athletic individuals, we recruited three distinct groups of young male subjects. Twenty were nationally ranked water polo players, 19 were engaged in weight-training programs, and 20 subjects comprised a nonexercising comparison group. All participants had measurements of spinal trabecular and integral bone density by quantitative computed tomography as well as a determination of hip bone density by dual photon absorptiometry. A series of potential predictor variables included maximal O2 uptake, back strength, leg strength, total kilocalories expended per day, body mass index, paraspinous muscle cross-sectional area, percent body fat, daily calcium intake, and age. We found no significant differences for any of the bone density measures between the two groups of athletic subjects, whereas bone density was generally significantly lower among the nonexercisers compared with either exercise group. Correlation analysis found only weak and somewhat inconsistent relationships when each of the subgroups was examined separately; however, when all subjects were assessed collectively, many more correlations reached significance. Paraspinous muscular area was found to be most robust in this regard, being significantly correlated with all three bone density measures (r = 0.33-0.55). By using step-wise regression analysis in each subgroup, we observed a consistent significant contribution (R2 = 0.18-0.44) of paraspinous muscle area to the variability in bone density at the spine and the hip. When the data of all three subgroups were pooled, regression analysis reconfirmed the importance of the muscle parameter (R2 = 0.06-0.27) to bone density variation, but more importantly it showed that differentiation based on exercise status was most significant (R2 = 0.18-0.22).

Adolescent↗

PubMed1988

Comment on the assessment of bone mineral status in children.

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Adolescent↗

PubMed1988

An examination of the association between vertebral deformities, physical disabilities and psychosocial problems.

In order to measure the clinical consequences of spinal osteoporosis, we correlated a number of physical and psychosocial dysfunctions with the degree of vertebral deformity in 204 women aged 55-75 yr. We employed 5 standardized questionnaire instruments: the physical dimension of the Sickness Impact Profile (SIP), an analog back pain scale, a 24-question instrument eliciting back-related disabilities, and assessments of self-esteem and mastery. Using these results as the dependent variables, we performed 5 separate stepwise regression analyses; independent variables were vertebral deformity score and 11 possible confounders. Using Pearson correlation coefficients, we found a high degree of correlation between each of the 5 primary outcome variables. Vertebral deformity score played a small but statistically significant role in the 3 models whose dependent variable was related to physical dysfunction, but it accounted for only 4-10% of the variance of these models. Mastery and self-esteem were related to overall poor health and attendant physical disabilities but not to vertebral deformity score. In this selected cohort of women, the occurrence of mild to moderate vertebral deformities caused little loss of physical function or function of psychosocial problems because of vertebral deformity. Although we were able to demonstrate a statistically significant handicap related to the total vertebral deformity score, several other clinical variables appeared to have a greater impact.

Aged↗

PubMed1988

Avascular necrosis of the femoral head: high-field-strength MR imaging with histologic correlation.

Magnetic resonance (MR) images, contact radiographs, and histologic sections of six femoral head specimens with avascular necrosis were correlated. A low-signal-intensity band or ring represented the repair tissue interface surrounding a high-signal-intensity necrotic marrow segment. Large segmental areas of low signal intensity were observed on T1-weighted images when the lesion consisted of necrotic bone with amorphous marrow debris and adjacent thickened trabecular bone with mesenchymal repair tissue infiltration. On intermediate-weighted images, however, mesenchymal repair tissue, which was located inferior to the necrotic zone, increased markedly in signal intensity, permitting distinction from low-intensity necrotic bone with amorphous marrow debris. When trabecular thickening with collapse predominated, segmental areas of low signal intensity with both sequences were found. MR signal intensities used in combination with anatomic configuration and location may provide information of potential therapeutic importance regarding tissue composition and stage of disease.

Adult↗

PubMed1987

Does exercise prevent osteoporosis?

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Bone and Bones↗

PubMed1987

Quantitative computed tomography: update 1987.

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Bone and Bones↗