Citations

Abstract We describe a young woman who acquired a painful, diffuse osteosclerosis of the cervical, thoracic, and lumbar spine, pelvis, and long bones of the legs as an adult. Bone densitometry showed a large increase in apparent bone density. Skeletal radiographs demonstrated progressive endosteal and periosteal thickening of the cortices. A bone scan showed increased uptake of radiolabel. The serum total alkaline phosphatase and 1,25-(OH)2D3 levels were substantially elevated and the immunoreactive PTH was mildly elevated. Bone biopsy showed increased bone turnover, especially on endocortical and intracortical surfaces, but the structural indices were normal. By 4 years after presentation the bone pain had remitted and the serum alkaline phosphatase, 1,25-(OH)2D3, and PTH were normal. No cause for the occurrence of osteosclerosis in this patient could be found.

Abstract The concept that vertebral fractures are caused by excessive loss of cancellous bone has been challenged by a recent study (J Bone Min Res 2:221, 1987) suggesting that vertebral bodies are composed mainly of cortical bone rather than cancellous bone. To resolve disagreement we used two independent methods to quantify the proportions of cortical and cancellous bone in 400 μm thick sections of the bodies of the second lumbar vertebrae from six men (aged 21–58 years) and seven women (aged 25–58 years). Based on the ash weight of the manually dissected components, 80% of the total bone in men and 72% in women was cancellous bone. Based on computer-assisted scanning of sections with a microdensitometer, 81% of the total bone in men and 71% in women was cancellous bone. We conclude that the traditional concept is correct: the vertebral body is composed mainly of cancellous bone.

Abstract Periosteal cells were isolated from tibiae of adult male rats after collagenase treatment. Northern blot analysis of total cytoplasmic RNA extracted from the isolated periosteal cells was positive for expression of genes encoding the osteoblast marker proteins osteocalcin (BGP) and pre-pro-α2(I) chain of type 1 procollagen. The isolated periosteal cells were incubated with 1 nM [3H]testosterone ([3H]T) for up to 240 minutes and the reaction products separated by high-performance liquid chromatography. [3H]5α-dihydrotestosterone ([3H]DHT) was not detected in extracts of periosteal cell incubations. In contrast, [3H]DHT was produced in a time-dependent manner by cells from seminal vesicles. These results suggest that testosterone 5α-reductase activity is not expressed by osteoblasts in rat tibial periosteum and that the anabolic effects of androgens in this tissue are not mediated by locally produced DHT.

Abstract Much of the clinical research in osteoporosis is directed toward documenting a reduction in vertebral fracture rate, but there is considerable disagreement about defining and quantifying vertebral fractures. We have evaluated the technique of digitizing landmarks identified on lateral radiographs of thoracic and lumbar vertebrae and computing vertebral body area. Reduction in area indicates that fractures occurred. Radiographs from 10 patients with osteoporosis and vertebral fractures were obtained from each of two centers, Henry Ford Hospital (HFH) and Mayo Clinic (MC), and vertebral area for each individual in the complete set of 20 radiographs was calculated at each center. Measurements at the two centers differed by a multiplicative constant related to the method of recording landmarks on the radiographs that was estimated using 300 x-rays from HFH. After adjusting the MC areas for this multiplicative relationship, the average ratio of the HFH areas to the transformed MC areas of individual vertebrae (T4-L5) ranged from 0.98 to 1.06. The correlation between HFH and transformed MC areas for individual vertebrae averaged 0.85, with slopes between 0.87 and 1.00, intercept average -0.57. Within-patient rank correlation averaged 0.97. We conclude that radiographic digitization is a reliable and reproducible method of determining vertebral body dimensions that is suitable for evaluating radiographs obtained at different clinical sites and for comparison with normal data. This technique should prove useful for documenting the presence of a vertebral fracture that may not be readily apparent on visual inspection of radiographs and for monitoring serial changes in vertebral body dimensions in long-term epidemiologic and therapeutic studies.

Abstract To determine the accuracy of self-reported risk factors for osteoporosis, an age-stratified random sample of Rochester, MN, women was studied. Results from a structured face-to-face interview were compared with information documented in contemporary inpatient and outpatient health care records in the community. Using the × statistic to evaluate concordance of these two data sources, we found substantial agreement for a history of proximal femoral and distal forearm fractures, peptic ulcer disease, estrogen replacement therapy and oral contraceptive use, and cigarette and alcohol exposure. Moderate agreement was seen for histories of other age-related fractures, hysterectomy or oophorectomy, thyroidectomy, and use of thyroid supplements. Poor agreement was found for prior thyroid disease, gastrectomy, and corticosteroid or anticonvulsant use. This study demonstrates a need for greater attention to the quality of self-reported risk factor data in studies of bone loss and fractures.

Abstract Recent studies have indicated that neutral collagenase can be produced in bones of rats. In addition, it has been demonstrated by in vitro studies that the enzyme is likely secreted by osteoblasts. Cells of the osteoblastic tumor cell line UMR-106 can be stimulated to produce not only collagenase, but also collagenase inhibitor and plasminogen activator. However, it is conceivable that not all osteoblasts produce all of these proteins. In this study, in which UMR cells were maximally stimulated with PTH, only a subpopulation of cells was observed to produce enhanced levels of collagenase but all cells had the ability to synthesize plasminogen activator. Cells of the rat osteosarcoma line UMR-106-01 were stained for the presence of collagenase and tissue plasminogen activator using an immunohistochemical procedure. In many cases, the cells were exposed to monensin for the final 3 h of incubation as well as to the inducing agent PTH. Monensin prevented export of the enzymes, enabling them to be visualized within their cell of origin. Maximal stimulation of collagenase was demonstrated to occur 8 h after exposure to 10−8-10−7 M PTH. Under these conditions, 14-17% of the cells appeared to synthesize elevated amounts of collagenase (as determined by intense staining). Without PTH stimulation, there was a low level of collagenase in all cells, but < 1% of the cells stained heavily for the enzyme. In contrast, strong staining for plasminogen activator was observed in all cells with or without PTH treatment. This suggests that the regulation of collagenase production in osteoblasts occurs at the level of the individual cell such that there appear to be subpopulations of cells that respond differently to PTH stimulation.

AbstractOver the last 25 years, the perceived clinical spectrum of primary hyperparathyroidism (HPT) has changed dramatically from a disorder characterized by severe bone and renal disease to one typically manifested by few or mild symptoms and little evidence of organ damage. Reasons for this change in spectrum include changing demographics (primary HPT is primarily a disease of the middle-aged and elderly), diffusion of medical knowledge leading to a higher index of suspicion, and improved clinical laboratory technology (especially inexpensive and accurate determination of serum calcium and parathyroid hormone). In the first 343 cases of primary HPT seen at the Massachusetts General Hospital, 57% had renal stones, 23% had hyper-parathyroid bone disease, and < 1% had no symptoms. By contrast, studies dating from the availability of automated serum calcium measurement found renal stones and hyperparathyroid bone disease in < 5% of cases, and about half of cases had few or no symptoms. Most patients with primary HPT today have mild, nonspecific symptoms, such as weakness, fatigue, and mental depression, and such signs as arterial hypertension and osteopenia, and detection of their hypercalcemia is generally serendipitous. The mildness and slow progression seen in many cases of primary HPT has resulted in much controversy about appropriate management.

Abstract The impact of primary hyperparathyroidism (HPT) on the population has not been well documented, and even less information is available for asymptomatic HPT. Only 57 deaths were attributed to the condition in the United States in 1986, for a reported HPT death rate of 0.24 per million per year. Many more patients were affected, however, and the incidence of hospitalization for HPT was 6.6 per 100,000 in 1986, counting all listed diagnoses, and 2.9 per 100,000 counting only first-listed diagnoses. Surgery was performed on approximately 10,000 hospitalized patients in the United States in 1986, for a parathyroidectomy rate of about 4.2 per 100,000 per year. When nonhospitalized cases are included, the rates are even higher. The estimated annual incidence of HPT was 42.1 per 100,000 in Rochester, Minnesota in 1974–1976; the prevalence of HPT was 4.3 per 1000 in a population survey in Sweden. By any of these measures, HPT is more common in women than men and increases with aging in both sexes. The potential cost of HPT could be as high as $420 million/year in the United States, but no formal estimates have been made. Disability related to HPT or its treatment has not been quantified; randomized clinical trials to determine the utility of parathyroidectomy have not been performed; and no assessment of cost benefit or cost effectiveness of any therapeutic modality has been carried out. Until patient management and cost issues are resolved, it is premature to consider an aggressive program to screen the general population for HPT.