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S J Silverberg

Publications and source records attributed to S J Silverberg.

At least 37 records · Page 2Linked to original sources

Osteoporosis in lung transplantation candidates with end-stage pulmonary disease.

PURPOSE: Fractures, a common complication of cardiac and liver transplantation, have not been reported in association with lung transplantation. However, many patients with end-stage pulmonary disease have multiple risk factors for osteoporosis, and several studies have suggested that osteoporosis before transplantation may increase the risk of fracture after transplantation. Therefore, we evaluated a group of patients with end-stage pulmonary disease who were awaiting lung transplantation to determine the prevalence of osteoporosis. METHODS: Seventy patients (aged 18-70 years) were evaluated consecutively with bone densitometry by dual-energy x-ray absorptiometry. The patients were predominantly Caucasian (96%). Bone mass was expressed as bone mineral density (BMD; g/cm2), as the number of standard deviations (SD) below peak bone mass (T score), and as bone mineral apparent density (BMAD; g/cm3), a measurement that minimizes the effects of bone size on BMD. Spine radiographs were obtained in a subset of 50 consecutive patients to detect vertebral compression fractures. Vitamin D status was assessed with serum concentrations of 25-hydroxyvitamin D. The patients were sorted into groups by pulmonary diagnosis: chronic obstructive pulmonary disease (COPD; n = 28); cystic fibrosis (n = 11); idiopathic pulmonary fibrosis; and other lung diseases (Other; n = 31). RESULTS: In the group as a whole, osteoporosis (T score below -2.5) was present in 30% of the patients at the lumbar spine and 49% at the femoral neck. Osteopenia (T score between -1 and -2.5) was present in an additional 35% at the lumbar spine and 31% at the femoral neck. The average femoral neck T score of patients with COPD and cystic fibrosis fell into the osteoporotic range (-2.7 +/- 0.3 and -2.6 +/- 0.3, respectively), significantly (P < 0.01) below that of the patients in the Other category (-1.5 +/- 0.3). The average lumbar spine T score fell into the osteopenic range in all three groups. Low BMAD in patients with cystic fibrosis confirmed that their low BMD was not due to their smaller body size. The prevalence rate of vertebral fractures was 29% in patients with COPD and 25% in those with cystic fibrosis. Vitamin D deficiency (25-hydroxyvitamin D levels < or = 10 ng/ml) was present in 36% of patients with cystic fibrosis and 20% with COPD and Other lung diseases. Lumbar spine BMD tended to be lower in cystic fibrosis patients with vitamin D deficiency. Patients with exposure to glucocorticoids (n = 46) had significantly more vertebral fractures (P < 0.05) and duration of exposure correlated negatively with lumbar spine BMD (r = -0.398; P = 0.008). COPD and Other patients not on glucocorticoids had mild lumbar spine osteopenia (0.972 +/- 0.06 g/cm2; T = -1.2 +/- 0.6). Very few of the patients on glucocorticoids were on any regimen to prevent osteoporosis. CONCLUSIONS: Osteoporosis and vitamin D deficiency are extremely common in patients with end-stage pulmonary disease. Only 34% of patients had normal lumbar spine BMD and only 22% had normal BMD at the hip. Patients with cystic fibrosis and glucocorticoid-treated patients with COPD were most severely affected. Therapies to prevent bone loss and treat established osteoporosis are uncommonly utilized in glucocorticoid-treated patients with end-stage pulmonary disease. Candidates for lung transplantation should be evaluated for osteoporosis and vitamin D deficiency at the time of acceptance to the transplant waiting list.

Absorptiometry, Photon↗

Vertebral osteopenia: a new indication for surgery in primary hyperparathyroidism.

Most patients with primary hyperparathyroidism have reduced radial and preserved vertebral bone density. We have identified a subset of patients with low lumbar spine bone density at diagnosis. This study assessed the effect of parathyroidectomy (undertaken based upon accepted surgical guidelines) or nonintervention on bone mineral density (BMD) in these patients. Twenty-two of 143 (15%) patients with mild primary hyperparathyroidism had lumbar spine BMD more than 1.5 SD below the mean for an age- and sex-matched population (z-score). Fourteen underwent parathyroidectomy, whereas 8 were followed with no intervention. All had annual BMD measurements for 4 yr after enrollment or after surgery. After parathyroidectomy, there was a brisk sustained rise in lumbar spine BMD [yr 1, 15 +/- 3% (P < 0.005); yr 4, 21 +/- 4% (P < 0.01)]. In those followed without surgery, BMD did not change significantly at any site. Postmenopausal women showed the same pattern as the cohort as a whole, i.e. increased BMD after surgery [yr 1, 13 +/- 3% (P < 0.01); yr 4, 16 +/- 5% (P < 0.01)], but no worsening was found with nonintervention despite the passage of years in the menopause. We conclude that parathyroidectomy markedly improves lumbar spine BMD in patients with vertebral osteopenia. It is proposed that reduced cancellous bone density should become a new indication for surgery in primary hyperparathyroidism.

Bone Density↗

Fracture after cardiac transplantation: a prospective longitudinal study.

Cardiac transplantation is associated with increased prevalence of vertebral fractures, but the natural history of and risk factors for fracture after this life-saving procedure are unclear. We evaluated 47 patients (34 men and 13 postmenopausal women) before transplantation with spinal radiographs, determination of bone density by dual energy x-ray absorptiometry, and measurement of biochemical indexes of mineral metabolism. During the first year after transplantation, incident fractures were documented radiographically. Associations among demographic characteristics, bone density, biochemistries, and fracture risk were evaluated with logistic regression analysis. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (400 IU/day), 17 patients (7 women and 10 men) sustained a total of 34 fractures. Most fractures involved the spine, and 85% of the patients who experienced fracture did so within 6 months of transplantation. Fifty-four percent of the women and 29% of the men experienced fracture. Femoral neck bone mineral density was significantly lower in women who experienced fracture than in those who did not (0.604 +/- 0.11 vs. 0.760 +/- 0.12 g/cm2; P < 0.04), but did not differ in men according to fracture outcome. The amount of bone loss at the femoral neck by 6 months after transplantation was significantly greater in men with fracture than in men without fracture (12.0 +/- 6.4% vs. 6.8 +/- 5.3%; P < 0.04), but did not differ in women according to fracture outcome. Pretransplant 1,25-dihydroxyvitamin D levels were significantly lower (25 +/- 9 vs. 39 +/- 17 pg/mL; P < 0.007) and intact PTH levels tended to be higher in men who did not experience fracture (37 +/- 15 vs. 69 +/- 46 pg/mL; P < 0.06). Individual pretransplant bone density measurements demonstrated substantial overlap between patients who did and did not experience fracture, and normal bone density did not necessarily protect against fracture after transplantation. We conclude that fractures are a common and early complication of cardiac transplantation. No pretransplant measurement has yet been identified that reliably predicts fracture after transplantation in the individual patient.

Bone Density↗

Bone structure in postmenopausal hyperparathyroid, osteoporotic, and normal women.

The purpose of this study was to test the hypothesis that patients with mild primary hyperparathyroidism are protected against postmenopausal (PM) loss of cancellous bone architecture. To achieve this, we compared bone structure and turnover in iliac bone biopsies from three groups: 16 women with mild primary hyperparathyroidism (PHPT; 58.2 +/- 2.2 years, 11.5 +/- 1.7 years PM), 17 women with untreated primary osteoporosis (OP; 65.1 +/- 2.0 years, 17.2 +/- 2.3 years PM), and 31 healthy women (N; 59.8 +/- 1.4 years, 13.4 +/- 1.5 years PM). The bone formation rate was significantly higher in PHPT than in either OP or N, and not different between OP and N. Cancellous bone volume, total strut length, and indices of connectivity (node number, node to node strut length, and node to terminus ratio) were significantly lower in OP than in either PHPT or N but were the same or higher in PHPT than in N. Indices of disconnectivity were significantly lower in PHPT than in N, whereas they were the same or higher in OP than N. The data were also analyzed in subgroups matched by years PM with no changes in the results. These findings indicate that osteoporotic patients with normal bone turnover have low bone volume and microarchitectural deterioration, while patients with mild PHPT have normal bone volume and normal or greater trabecular connectivity despite higher bone turnover. These findings suggest that mild PHPT protects against the loss of cancellous bone structure that normally follows menopause.

Bone and Bones↗

Longitudinal measurements of bone density and biochemical indices in untreated primary hyperparathyroidism.

A large number of patients with primary hyperparathyroidism today do not undergo parathyroidectomy. In this prospective study, we evaluated the effect of untreated disease on biochemical and bone densitometric indices. In 66 patients, seven annual measurements showed no change in serum calcium, phosphorus, PTH, vitamin D, or alkaline phosphatase; in urinary calcium, hydroxyproline or hydroxypyridinium cross-link excretion; or lumbar spine, femoral neck, and radial bone mineral density. The subset of postmenopausal women also showed no change in biochemical indices or bone density at any of the three sites. Twenty-four patients met guidelines for surgery as established by the NIH Consensus Conference, 1990. They differed from those who did not meet these guidelines only by being younger (50 +/- 3 vs. 62 +/- 2 yr; P = 0.0005) and by having higher urinary calcium excretion [7.7 +/- 0.9 vs. 5.4 +/- 0.3 mmol/L (310 +/- 37 vs. 215 +/- 14 mg/g creatinine); P < 0.01]. No longitudinal changes in biochemical profile or bone mineral density at any site were noted in this subgroup. Conservative management of patients with mild primary hyperparathyroidism does not lead to progression of disease, as reflected by biochemical indices. Bone density is maintained over 6 yr of observation at sites reflecting both cortical (radius) and cancellous (lumbar spine) bone.

Adult↗

Increased bone mineral density after parathyroidectomy in primary hyperparathyroidism.

Skeletal involvement in primary hyperparathyroidism is characterized by preferential loss of cortical bone, whereas cancellous bone is relatively spared. Little data are available concerning changes in bone density, particularly at sites containing more cancellous bone, after successful parathyroidectomy. Most patients with primary hyperparathyroidism are asymptomatic, but approximately 50% meet one or more criteria for surgery. In a prospective study of 34 patients who met one or more such criteria, bone density rose at all skeletal sites (lumbar spine, femoral neck, and the radius) in the 4 yr after surgery. The lumbar spine, with most cancellous bone, showed a rapid (mean +/- SE, yr 1, 8.2 +/- 2.0%; P < 0.005) and sustained (yr 4, 12.8 +/- 2.8%; P < 0.001) rise. Post-menopausal patients were similar (by yr 4, 12.5 +/- 2.7%; P < 0.005). At the femoral neck, with intermediate cancellous and cortical composition, a similar increase was noted (12.7 +/- 3.8% by yr 4; P < 0.01). The distal radius, containing mostly cortical bone, rose modestly (4.0 +/- 1.5% by yr 3; P < 0.05), except in patients with lowest preoperative bone density, where the increase was marked (12.3 +/- 2.6% by yr 3; P < 0.05). In patients meeting surgical guidelines, parathyroidectomy is associated with improved bone mineral density.

Adult↗

Osteoporosis after cardiac transplantation.

PURPOSE: The purpose of this study was to determine the prevalence of osteopenia and fractures and to describe the biochemical indices of mineral metabolism in patients who have undergone cardiac transplantation. PATIENTS AND METHODS: Forty adult patients who had received a cardiac transplant between 1982 and 1990 and who were receiving immunosuppressive therapy with prednisone and cyclosporine A were studied. Bone densitometric measurements by dual-energy x-ray absorptiometry of the lumbar spine and femoral neck and radiographs of the thoracic and lumbar spine were obtained for all patients. Routine serum and urine biochemical values as well as more specialized biochemical analyses (intact parathyroid hormone, metabolites of vitamin D, and osteocalcin) were obtained. RESULTS: Osteopenia was present in 28% of the patients at the lumbar spine and 20% of the patients at the femoral neck. Vertebral fractures were present in 35% of patients. In contrast to other patients receiving glucocorticoids, serum osteocalcin, a marker of bone formation, was elevated in 60% of patients. CONCLUSIONS: Osteopenia and vertebral fractures are common in patients after cardiac transplantation. The presence of elevated osteocalcin levels suggests that the pathogenesis of the osteoporosis in these patients differs from that of glucocorticoid-induced osteoporosis.

Absorptiometry, Photon↗

Maintenance of cancellous bone connectivity in primary hyperparathyroidism: trabecular strut analysis.

We previously demonstrated an increase in cancellous bone volume and trabecular number in patients with mild primary hyperparathyroidism (PHPT). To test the hypothesis that this increase is due to preservation of cancellous bone architecture, we conducted a trabecular strut analysis using a new method that measures trabecular connectivity. Iliac crest biopsies from 37 patients with PHPT, 14 men (28-68 years) and 23 women (26-68 years), were examined histomorphometrically and compared to cadaveric samples from 24 age-matched subjects, 17 men and 7 women. Two-dimensional indices of cancellous structure--node number (N.Nd), terminus number (N.Tm), node to node (Nd.Nd), node to terminus (Nd.Tm), and terminus to terminus (Tm.Tm) strut lengths, and total strut length (TSL)--were measured and the ratio of node number to terminus number (N.Nd/N.Tm) calculated. TSL, N.Nd, and Nd.Nd were significantly higher in patients than in controls. TSL and Nd.Nd, but not N.Nd or Nd/Tm, decreased significantly with age in PHPT, indicating that age-related bone loss in PHPT occurs without significant loss of trabecular connectivity. Two-dimensional indices reflecting connectivity or the amount of bone, that is, N.Nd, Nd.Nd, N.Nd/N.Tm, and TSL, correlated positively with cancellous bone volume (BV/TV) and trabecular number (Tb.N) and negatively with trabecular spacing (Tb.Sp) in both PHPT and controls. Trabecular thickness (Tb.Th) correlated positively with Nd.Nd and Tb.N and negatively with Tm.Tm in PHPT but not in controls. The present data show that in PHPT there is not only greater cancellous bone volume and trabecular number but preserved trabecular connectivity as well. The data further support the hypothesis that in PHPT cancellous bone architecture is maintained.

Adult↗

Urinary hydroxypyridinium cross-links of collagen in primary hyperparathyroidism.

Urinary concentrations of the collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), were determined in 87 patients with untreated or surgically treated primary hyperparathyroidism (PHPT). Eighty-four healthy individuals, matched for age and sex, constituted the control group for the excretion of pyridinium cross-links. In addition, a subgroup of 25 patients with PHPT was followed longitudinally for up to 2 yr after successful parathyroidectomy. Mean urinary excretion of PYD (46.8 +/- 2.7 nmol/mmol creatinine) and DPD (17.6 +/- 1.3 nmol/mmol creatinine) was significantly higher in patients with untreated PHPT than in normal subjects (P less than 0.001). In the group undergoing successful parathyroidectomy, mean urinary concentrations of PYD (34 +/- 2.5) and DPD (9.4 +/- 0.8) were similar to those in normal controls and significantly lower than those in the untreated patient population (P less than 0.001). The urinary concentration of both cross-links was significantly correlated with serum levels of both alkaline phosphatase and PTH. Mean urinary concentrations of both cross-link compounds decreased significantly within 6 months in patients followed longitudinally and as early as 2 weeks after surgery in individual patients compared to presurgical baseline values. These changes preceded the reduction in serum alkaline phosphatase and hydroxyproline by approximately 6 months. The results demonstrate that urinary hydroxypyridinium cross-links of collagen are useful indices in the clinical assessment of bone involvement in PHPT.

Alkaline Phosphatase↗

Characterization and evaluation of asymptomatic primary hyperparathyroidism.

Data are presented on 97 patients with primary hyperparathyroidism who constitute a representative cohort of the disease seen today. The average calcium (11.1 +/- 0.1 mg/dl; normal 8.7-10.7), phosphorus (2.8 +/- 0.1 mg/dl; normal 2.5-4.5), and parathyroid hormone level by immunoradiometric assay (119 +/- 7 pg/ml; normal 10-65) are typical of the modern presentation of primary hyperparathyroidism. Most patients were asymptomatic in that there was evidence for nephrolithiasis in only 18% and for radiologically evident bone disease in only 1% of patients. Nevertheless, when patients were evaluated with bone densitometry and with histomorphometric analysis of the bone biopsy specimen, evidence for the hyperparathyroid process could be shown in the majority of patients. Selective reduction of cortical bone and preservation of cancellous bone were apparent. Among patients with nephrolithiasis, no particular feature distinguished them from patients without nephrolithiasis. All biochemical data were similar between both stone and non-stone formers. The selective reduction in cortical bone was seen to the same extent among those with stones as among those without stones. The average 1,25-dihydroxyvitamin D level was not increased among those with stones. When the population was divided into groups with elevated or normal 1,25-dihydroxyvitamin D levels, the incidence of nephrolithiasis was unchanged. The results indicate that bone involvement can be demonstrated among most patients with asymptomatic primary hyperparathyroidism and that no pathophysiologic mechanisms are yet apparent to account for nephrolithiasis in primary hyperparathyroidism.

Adult↗

Nephrolithiasis and bone involvement in primary hyperparathyroidism.

PURPOSE: The purpose of this study was to compare patients with primary hyperparathyroidism with and without nephrolithiasis with regard to (1) biochemical profile, and (2) presence and extent of bone involvement. PATIENTS AND METHODS: Of 70 unselected patients enrolled in a longitudinal study on the natural history of primary hyperparathyroidism, 62 who underwent complete bone densitometry evaluation were considered. The patients had mild hypercalcemia (2.77 +/- 0.02 mmol/L), as well as elevated parathyroid hormone levels by mid-molecule, N-terminal, and immunoradiometric assays. Bone densitometry was assessed by dual-photon absorptiometry of the lumbar spine and femoral neck, and single-photon absorptiometry of the forearm. RESULTS: Eleven of the 62 patients (18%) had nephrolithiasis. There was no difference in serum parathyroid hormone levels, calcium, phosphorus, serum 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D3 between those with and without kidney stones. Total daily urinary calcium excretion was higher among those who formed stones (8.2 +/- 1.0 mmol versus 6.1 +/- 0.4 mmol, p less than 0.05), but not when expressed per mmol of creatinine (0.72 +/- 0.07 versus 0.69 +/- 0.04). Urinary hydroxyproline was also higher in patients who formed stones (58 +/- 11 mg/24 hours versus 37 +/- 2 mg/24 hours; p less than 0.05). Hypercalciuria occurred in 39% of the entire cohort (n = 24), and in 33% (n = 17) of those without stones. Only 29% (n = 7) of those with hypercalciuria had nephrolithiasis. Calcium excretion correlated positively with serum 1,25-dihydroxyvitamin D3 (r = +0.32, p less than 0.05), and negatively with forearm bone mineral density (all patients: r = -0.34, p less than 0.05; hypercalciuric patients: r = -0.53, p less than 0.05). Circulating 1,25-dihydroxyvitamin D3 levels were elevated in a similar proportion of (1) all patients (31%, n = 19); (2) those with nephrolithiasis (27%); and (3) those without stones (31%). Bone mineral density was less than 80% of normal in 61% of patients, but forearm, femoral neck, and lumbar spine density were indistinguishable among those with and without stones. CONCLUSIONS: Cortical bone demineralization occurs to the same extent and frequency in patients with and without nephrolithiasis, and these two subgroups share similar biochemical and bone densitometric profiles. The pathophysiologic events leading to renal and skeletal involvement in primary hyperparathyroidism may be less selective than previously believed, as evidenced by: (1) increased urinary hydroxyproline in patients with nephrolithiasis, and (2) documentation that urinary calcium excretion reflects not only vitamin D status, but bone resorption was well.

Bone Density↗

The histomorphometry of bone in primary hyperparathyroidism: preservation of cancellous bone structure.

To evaluate the effects of primary hyperparathyroidism (PHPT) on bone mass and structure, we have studied the iliac crest biopsies of 27 patients, 10 males (28-68 yr old) and 17 females (26-72 yr old) with mild PHPT after in vivo tetracycline labeling. All patients had mild hypercalcemia in the absence of any other cause and elevated levels of PTH without radiological evidence of bone disease. Static parameters of bone turnover (osteoid surface, osteoid volume, and eroded surface) were elevated in both men and women compared to normal values; the midmolecule RIA for PTH (PTHMM) was positively correlated with osteoid surface (r = 0.44; P less than 0.025) and eroded surface (r = 0.58; P less than 0.005). Dynamic parameters of bone turnover (mineralizing surface, expressed as double plus half single labeled surface, and bone formation rate at tissue level) were elevated compared to normal values; PTHMM was positively correlated with double plus half single labeled surfaces (r = 0.33; P less than 0.05) and with bone formation rate at the tissue level (r = 0.37; P less than 0.05). The mineral apposition rate was within the limits of normal values and positively correlated with PTHMM (r = 0.34; P less than 0.05). Histomorphometric parameters of bone structure [cancellous bone volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), cortical thickness (Ct.Th), and total bone density (TBD)] were compared to those in 20 autopsy control subjects, 12 men (33-60 yr old) and 8 women (27-75 yr old). BV/TV and Tb.N were significantly higher in PHPT patients than controls (P less than 0.02 and P less than 0.001, respectively). Tb.Sp was significantly lower in PHPT patients than controls (P less than 0.001), whereas Tb.Th was not significantly different between PHPT patients and controls. Ct.Th was significantly lower in PHPT patients than in controls (P less than 0.001), whereas TBD was not significantly different between the two groups. BV/TV was negatively correlated with age in both controls and PHPT patients. Tb.N showed a negative correlation and Tb.Sp a positive correlation with age in controls (r = -0.47; P less than 0.05 and r = 0.52; P less than 0.02, respectively), but they were not significantly dependent on age in PHPT patients. Tb.Th, while showing no significant age-related change in controls, was negatively correlated with age in PHPT patients (r = -0.42; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Suppression of parathyroid hormone secretion with oral calcium in normal subjects and patients with primary hyperparathyroidism.

Exquisite sensitivity of normal parathyroid glands to small changes in ambient calcium concentrations and impaired sensitivity in primary hyperparathyroidism have been shown in vitro. Using an assay for PTH that detects rapid changes in PTH secretion (N-terminal-specific RIA; normal range, less than 3-33 pg/mL), we determined PTH suppressibility in response to a standardized dose of oral calcium in normal subjects and patients with primary hyperparathyroidism. Nine normal subjects were given oral calcium (25 mg/kg), and blood was analyzed half-hourly for 3 h for calcium and N-terminal PTH (N-PTH). Serum calcium rose by 0.34 +/- 0.06 mg/dL (0.085 +/- 0.015 mmol/L), and N-PTH levels declined rapidly from 15.3 +/- 1.4 to 4.2 +/- 1.1 pg/mL (-73 +/- 6%; P less than 0.01). In six subjects N-PTH concentrations became undetectable. Nine patients with primary hyperparathyroidism were tested in the same manner. Serum calcium rose by 0.53 +/- 0.1 mg/dL (0.13 +/- 0.025 mmol/L), and N-PTH levels declined less, from 66 +/- 14 to 52 +/- 12 pg/mL (-21 +/- 4%; P less than 0.05). In none of the patients was the PTH reduced to less than 20 pg/mL. These results illustrate in vivo that the PTH response to oral calcium in primary hyperparathyroidism is markedly different from that in normal subjects.

Administration, Oral↗

Bone disease in primary hyperparathyroidism.

The classic bone disease of primary hyperparathyroidism, osteitis fibrosa cystica, was characterized by subperiosteal bone resorption, osteopenia, and "brown tumors." Since the description of this skeletal disorder, the clinical profile of primary hyperparathyroidism has evolved markedly. The disease today is often characterized by no more than asymptomatic hypercalcemia, and severe bone disease is a distinct rarity. However, as we have endeavored to show in this article, newer and more sensitive techniques show significant evidence of the effect of excess parathyroid hormone on the skeleton. Bone density as measured by photon absorptiometry and bone histomorphometry show a deficit of cortical bone and a preservation or increase in cancellous bone elements in mild primary hyperparathyroidism with no clinical evidence of skeletal disease. Important questions exist as to the therapeutic implications of these data. Does the presence of parathyroid hormone effect on sophisticated testing portend the development of clinical bone disease? Should these data be used as a rationale for surgical intervention in patients who might otherwise be followed conservatively with mild primary hyperparathyroidism? The answers to these questions must await further data collection and study.

Bone Diseases↗

Abnormalities in parathyroid hormone secretion and 1,25-dihydroxyvitamin D3 formation in women with osteoporosis.

We investigated the parathyroid hormone-1,25-dihydroxyvitamin D3 (1,25(OH)2D) axis in osteoporosis by administering phosphate to 8 postmenopausal women with osteoporosis (49 to 78 years old) and to 10 normal women matched for age (50 to 74 years). All subjects responded with a similar increase in the serum phosphorus concentration (women with osteoporosis, 1.15 +/- 0.06 to 1.79 +/- 0.09 mmol per liter; controls, 1.14 +/- 0.05 to 1.73 +/- 0.08 mmol per liter) and a fall in the ionized calcium concentration (women with osteoporosis, 1.12 +/- 0.03 to 1.06 +/- 0.03 mmol per liter; controls, 1.17 +/- 0.01 to 1.11 +/- 0.02 mmol per liter). Parathyroid hormone levels rose 2.5-fold in the control group (15.4 +/- 2.2 to 37.9 +/- 6.1 pg per milliliter) but increased by only 43 percent in the group with osteoporosis (14.8 +/- 2.8 to 21.2 +/- 4.1 pg per milliliter), an increase similar to that previously reported in young normal subjects (53 percent). In healthy older and younger subjects, the levels of 1,25(OH)2D did not change; in the subjects with osteoporosis, however, they decreased significantly (50 percent). We conclude that older women require a greater parathyroid hormone stimulus than younger women to maintain vitamin D homeostasis, because of an age-related decline in the formation of 1,25(OH)2D in response to parathyroid hormone, and that in osteoporosis the age-appropriate parathyroid hormone response to the same hypocalcemic signal is diminished. Our results are consistent with the presence of an abnormality in parathyroid hormone secretory function in osteoporosis in addition to the universal decline in 1,25(OH)2D responsiveness associated with aging.

Aged↗

Skeletal disease in primary hyperparathyroidism.

Most patients with primary hyperparathyroidism in the 1980s do not have evidence of bone disease when they are evaluated by conventional radiography. We sought to determine whether skeletal involvement can be appreciated when more sensitive techniques, such as bone densitometry and bone biopsy, are utilized. We investigated 52 patients with primary hyperparathyroidism. They had mild hypercalcemia, 2.8 +/- 0.03 mmol/liter (11.1 +/- 0.1 mg/dl), low normal phosphorus, 0.9 +/- 0.03 mmol/liter (2.8 +/- 0.1 mg/dl), and no symptoms or specific radiological signs of skeletal involvement. The greatest reduction in bone mineral density was found at the site of predominantly cortical bone, the radius (0.54 +/- 0.1 g/cm; 79 +/- 2% of expected), whereas the site of predominantly cancellous bone, the lumbar spine (1.07 +/- 0.03 g/cm2), was normal (95 +/- 3% of expected). The site of mixed composition, the femoral neck (0.78 +/- 0.14 g/cm2), gave an intermediate value (89 +/- 2% of expected). Preferential involvement of cortical bone with apparent preservation of cancellous bone in primary hyperparathyroidism was confirmed by percutaneous bone biopsy. Over 80% of patients had a mean cortical width below the expected mean, whereas cancellous bone volume in over 80% of patients was above the expected mean. The results indicate that the majority of patients with asymptomatic primary hyperparathyroidism have evidence by bone densitometry and bone biopsy for cortical bone disease. The results also indicate that the mild hyperparathyroid state may be protective of cancellous bone. The therapeutic implications of these observations await further longitudinal experience with this study population.

Biopsy↗