Wall thickness, a major determinant of trabecular thickness, falls with age and falls further in osteoporosis. To estimate the importance of defective osteoblast recruitment in the pathogenesis of this defect, we compared various histologic indices of bone formation in iliac bone biopsies in three groups of subjects--healthy premenopausal women, healthy postmenopausal women, and patients with postmenopausal osteoporosis and at least one non-traumatic vertebral compression fracture. Indices that reflect the frequency of activation of bone remodeling and consequent birth rate of new teams of osteoblasts (osteoid surface, mineralizing surface, osteoblast surface, and bone formation rate, all expressed per unit of bone surface) were each higher in healthy subjects who were postmenopausal than in those who were premenopausal, but lower in osteoporotic than in normal postmenopausal women. In each group, the primary surface measurements were significantly correlated with each other, but the correlation was less close in those with osteoporosis. Indices that reflect the average collective performance of individual teams of osteoblasts (mineralizing surface and osteoblast surface per unit of osteoid surface, mineral apposition rate, adjusted apposition rate, and wall thickness) were all lower in postmenopausal than in premenopausal normal subjects, and even lower in those with postmenopausal osteoporosis. The parameters of the regression lines relating bone formation rate to osteoblast surface were essentially the same in each group, indicating that bone formation rate per unit of osteoblast surface was unaffected by age or menopause, and was the same in osteoporosis as in healthy subjects of similar age.(ABSTRACT TRUNCATED AT 250 WORDS)
The frequency distributions of mineral apposition rate (MAR) and mineralizing surface (MS), measured separately on the intracortical, endocortical, and cancellous surfaces in 46 normal subjects and 79 patients with postmenopausal osteoporosis, indicated that MAR has a finite lower limit of 0.3 mu/day (uncorrected for section obliquity) but that MS has no finite lower limit. We conclude that in the absence of labels MAR, and indices derived from it, must be treated as missing values, but that MS and indices with MS in the numerator should be allowed to take values of zero. To avoid infinite values for indices with MS in the denominator, we propose that osteoid mineralization rate (the reciprocal of mineralization lag time) and osteoblast vigor (the reciprocal of formation period) be used instead. For surfaces with genuine single labels (SL) but no double labels, we propose that MS is calculated as SL/2 and that for MAR either the lower limit of 0.3 or the mean measured value from other surfaces be used for calculating derived indices.
The relation of zinc to the aging skeleton was investigated in 140 women aged 36-85 years, mostly postmenopausal, who attended the Jerusalem Osteoporosis Center. Osteoporosis was determined by lumbar spine radiograms (Smith index). Bone density (BD) of the distal radius was assessed by Compton spectroscopy and bone mineral content (BMC) at the same site by single-photon absorptiometry. Urine samples (24 h) were analyzed for zinc (UZn), hydroxyproline (UHP), calcium (UCa), magnesium (UMg), and phosphorus (UP) and expressed per gram creatinine. Patients with definite osteoporosis (n = 94) compared to subjects with borderline or no osteoporosis (n = 34) had a significantly higher mean age (67.4 versus 58.6 years), postmenopausal age (PMA, 19.9 versus 11.0), UZn (811 versus 581), UHP (23.5 versus 18.2), and UMg (90.4 versus 74.3). Urinary calcium UCa and phosphorus UP were similar in both groups. The bone mass measurements BD, BMC, and CI were lower in the osteoporotic group. Hyperzincuria (UZn above 800 micrograms/g creatinine) was found in 41 osteoporotic patients (45%) compared to 6 subjects in the control group (17%). In view of the positive correlation between UZn and age (r = 0.35, p = 0.001) and to eliminate the effect of age, a separate analysis was performed for 66 subjects under the age of 65 in whom the mean age was similar for the osteoporosis patients (n = 38) and control group (n = 28). Nevertheless, the osteoporosis patients still had a significantly higher mean UZn and UHP.(ABSTRACT TRUNCATED AT 250 WORDS)
We measured the individual lengths of fluorescent labels on the three subdivisions of the endosteal envelope in iliac bone biopsy specimens produced by the administration of both oxytetracycline and demethylchlortetracycline. Fifty-one healthy subjects and 53 patients with postmenopausal osteoporosis were labeled in the stated order, and 8 osteopenic patients were labeled in the reverse order. Whatever the order of administration, the demethylchlortetracycline label was longer than the oxytetracycline label. We conclude: (1) the difference in label lengths reflects a difference between the two compounds in some intrinsic property, whether physical, chemical, or pharmacokinetic. (2) If the calculation of extent of mineralizing surface is based on the mean length of the two labels, a suitable correction should be applied to the shorter label; alternatively, the length of the longer label alone should be used. (3) Unlabeled osteoid not due to label escape probably results from slow terminal mineralization after cessation of matrix synthesis during which too few tetracycline molecules are incorporated to exceed the threshold for visible fluorescence, rather than from the temporary interruption of mineralization followed by its resumption.
We measured indices of bone volume (cancellous and cortical) and bone surface (cancellous, endocortical, and intracortical) in intact, full-thickness transiliac bone biopsies obtained from 47 healthy white women (23 premenopausal and 24 postmenopausal) and 82 patients with postmenopausal osteoporosis. In the normal subjects there was the expected loss of cancellous bone with age, best shown by a reduction in bone surface/tissue volume, but no fall in cortical thickness with age despite a significant reduction in forearm bone density measured by single-photon absorptiometry. Bone surface/bone volume was about four times higher in cancellous than in cortical bone, and cancellous bone contributed about one-third of the total bone volume and about two-thirds of the bone surface when related to the core volume referent. In the osteoporotic patients, core width, an index of iliac bone thickness at the biopsy site, was reduced by 10%, but we could not determine whether this was the result of compaction of the core or of bone slenderness. All indices of bone volume, cortical as well as cancellous, were significantly smaller, as were the values for forearm bone densitometry; the relative deficits at different sites depended on whether they were expressed as percentages or as zeta scores. Bone surface/bone volume was increased in both cancellous and cortical bone, but bone surface/tissue volume was reduced in cancellous bone and increased in cortical bone. The proportions of total bone volume and surface contributed by cancellous and cortical bone were almost the same as in normal postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)
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