Frailty and osteoporosis in older women--a prospective study.

UNLABELLED: Despite sharing common risk factors and biological pathways, the relationship between frailty and osteoporosis (OP) is not clear. This prospective study has shown that frailty defined by the Vulnerable Elders Survey can predict a decrease in bone mineral density after 1 year. Thus, frail older women should be assessed for osteoporosis. INTRODUCTION: Frailty and OP share common risk factors such as age, sarcopenia, lack of physical activity, low body weight, and smoking. Despite shared risk factors and biological pathways, the relationship between frailty and OP is not clear. The purpose of our prospective study was to examine this relationship in a community sample of older women. METHODS: A sample of 235 community-dwelling women was assessed for demographic, medical, frailty and OP status at baseline, and after at least 1 year. Frailty was assessed using the Cardiovascular Health study (CHS) frailty phenotype and using the Vulnerable Elders Survey (VES-13). OP was measured using dual photon absorptiometry bone mineral density (BMD). Descriptive statistics and regression models were used. RESULTS: At baseline, 235 women with a mean age of 77.6 (SD = 5.4), body mass index (BMI) of 28.3 (SD = 5.2) kg/m(2), and BMD of 0.7 (SD = 0.2) g/cm(2)were assessed. No correlation was found between BMD and the CHS (BMD spine, r = 0.009, p = 0.889; BMD hips, r = 0.050, p = 0.473) or the VES-13 (BMD spine, r = 0.034, p = 0.605; BMD hips, r = -0.042, p = 0.537) frailty scales. One hundred fifty-two (63.9 %) women were assessed after 1 year. In a regression model, women who were frail at baseline (VES-13) were found to have a statistically significantly lower hip and spine BMD at follow-up (controlling for BMI) than women who were non-frail at baseline (p = 0.0393, hip; p = 0.0069, spine). CONCLUSIONS: Frailty status as defined by the VES-13 predicts a decrease in BMD after 1 year.

Higher prevalence of osteoporosis among female Holocaust survivors.

UNLABELLED: The prevalence of osteoporosis was statistically significantly higher among female Holocaust survivors than among those who were not exposed to the Holocaust. These findings support the importance of nutrition and environmental conditions during childhood and adolescence on BMD in older adults. INTRODUCTION: Holocaust survivors during childhood and adolescence experienced undernutrition and lack of exercise and sunlight. The study aimed to establish if Holocaust survivors have higher prevalence of osteoporosis than subjects who were not Holocaust survivors. METHODS: Seventy-three female Jewish Holocaust survivors > or = 60 years old and 60 female European-born Jews > or =60 years old who were not in the Holocaust were examined. BMD was measured using DXA of the lumbar spine and hips. The Cochran-Armitage trend test was used to test for an increasing trend in decreased BMD in the Holocaust survivors versus controls. RESULTS: Among Holocaust survivors 54.8% had osteoporosis, 39.7% osteopenia, and 5.5% normal BMD, whereas among controls 25.0% had osteoporosis, 55.0% osteopenia, and 20.0% normal BMD (p = 0.0001). In those who were <17 years old in 1945, among Holocaust survivors 58.0% had osteoporosis, 34.0% osteopenia, and 8.0% normal BMD, whereas among controls 20.0% had osteoporosis, 57.8% osteopenia, and 22.2% normal BMD (p = 0.0003). In those > or =17 years old in 1945, among Holocaust survivors 47.8% had osteoporosis, 52.2% osteopenia and none had normal BMD, whereas among controls 40.0% had osteoporosis, 46.7% osteopenia, and 13.3% normal BMD (p = 0.28). CONCLUSION: The prevalence of osteoporosis was significantly higher among Holocaust survivors.

Alfacalcidol (alpha D3) and calcium in osteoporosis.

In a prospective, randomized study, 66 osteoporotic postmenopausal women (mean age, 67 years) were scheduled to receive either alfacalcidol 0.25 microgram twice daily together with calcium 500 mg twice daily (treatment group, n = 24) or placebo twice daily with calcium 500 mg twice daily (control group, n = 42) for three years. In the treatment group, bone mineral content at the distal radius may have increased by 2% compared to a significant decrease of 7.8% in the control group. The difference between the two groups was also significant. Since the dose of alfacalcidol and calcium remained unadjusted, frequent hypercalciuria, as well as occasional mild, transient elevations of serum calcium, were observed in the treatment group. No changes in serum creatinine levels or creatinine clearance throughout the study were observed. The two groups did not differ with respect to the frequency of clinical side effects, which were mainly gastrointestinal and probably related to the calcium supplementation. Alfacalcidol and calcium may prevent further bone loss in women suffering from postmenopausal osteoporosis.

Heterogeneous size of the parathyroid glands in familial multiple endocrine neoplasia type 1.

OBJECTIVE: We wished to determine whether there was size heterogeneity of the parathyroid glands in patients with familial multiple endocrine neoplasia type 1 (FMEN1) and primary hyperparathyroidism. DESIGN: At the National Institutes of Health we performed a retrospective analysis of parathyroid gland volume either from initial or repeat parathyroid exploration. PATIENTS: We studied subjects with FMEN1 and primary hyperparathyroidism. MEASUREMENTS: The parathyroid gland volume was estimated from recorded orthogonal diameters. Volume could also be estimated conservatively in many glands for which one or more diameters were not recorded. Reproducibility of volume measurements was tested with a series of clay gland models. Indices of variability (among glands at an operation or among replicate measurements of a clay model) were the ratio of maximum volume/minimum volume and the average standard deviation of the log volume. RESULTS: The most complete data were from eight initial operations with three dimensions recorded for all four glands. Volume heterogeneity was indicated by the average ratio of 9.6 for the maximum/minimum gland volume within an operation. The size heterogeneity was even greater among other subgroups. For example, the average ratio of maximum/minimum gland volume within an operation was 17 among five initial operations with four glands removed, but lacking measurements of three dimensions for some glands. Little of this size heterogeneity could be attributed to measurement error since eight replicate measurements on a model gland yielded a maximum/minimum volume ratio of 1.45. CONCLUSIONS: There is a wide heterogeneity in size of the parathyroid glands in the patients with FMEN1 and primary hyperparathyroidism.

Histomorphometric analysis of weight bearing bones of diabetic and non-diabetic sand rats (Psammomys obesus).

Femoral and tibial bones of diabetic sand rats were compared to those of non-diabetic sand rats (Psammomys obesus) of the same age range. Three morphometric parameters were examined: trabecular bone volume, length of epiphyseal cartilage (proliferative and mature) and cortical thickness of mid-shaft of tibia. There were no statistically significant differences between the test and control animals for the last two parameters. By contrast the trabecular bone volume of the diabetic animals was less than half that of the control animals indicating a substantial loss of trabecular bone mass. This study suggests that Psammomys obesus is a suitable model for studying the effects of diabetes mellitus on bone mass, provided that weight bearing bones are used.

HLA-D antigens and Paget's disease of bone.

HLA-A, -B, -C, -DR, and -DQ antigens were determined in 25 Ashkenazi Jews with Paget's disease of bone. HLA-DR2 was more frequent in the Pagetic patients compared with 57 healthy controls of the same ethnic origin. This finding concurs with a previous report and raises the possibility that HLA-DR2 may be associated with Paget's disease of bone, probably by predisposing the bone cells to viral infection.

The effect of swimming on bone modeling and composition in young adult rats.

The purpose of this study was to investigate the adaptability of long bones of young adult rats to the stress of chronic aquatic exercise. Twenty-eight female Sabra rats (12 weeks old) were randomly assigned to two groups and treatments: exercise (14 rats) and sedentary control (14 rats) matched for age and weight. Exercised animals were trained to swim in a water bath (35 degrees +/- 1 degree C, 1 hour daily 5 times a week) for 12 weeks loaded with lead weights on their tails (2% of their body weight) (BW). At the end of the training period following blood sampling for alkaline phosphatase, all rats were sacrificed and the humeri and tibiae bones were removed for the following measurements: bone morphometry, bone water compartmentalization, bone density (BD), bone mineral content (BMC), and bone ions content (Ca, Pi, Mg, Zn). The results indicate that exercise did not significantly affect the animals' body weight, bone volume, or length and diameters. However, bone hydration properties, BD, bone mass, and mineralization revealed significant differences between swim-trained rats and controls (P less than 0.05). Longitudinal (R1) measurement was higher by 43% for both humerus and tibia, and Transverse (R2) relaxation rates of hydrogen proton were higher by 117 and 76% for humerus and tibia, respectively; fraction of bound water was higher by 36 and 46% for humerus and tibia, respectively. BD, bone weight, and ash were higher by 13%. BMC and bone ions content were higher by 10%, and alkaline phosphatase was higher by 67%.(ABSTRACT TRUNCATED AT 250 WORDS)

Progressive bone loss during long-term home total parenteral nutrition.

Metabolic bone disease occurs in patients receiving prolonged home total parenteral nutrition (HTPN). We studied bone-mass status in 10 patients (seven males, three females, age 19-66 years) who had been receiving HTPN for 0 to 67 months (mean 24 months), mostly for short-bowel syndrome. Four patients had spinal osteoporosis on radiograms. The density of various bone components at the wrist was measured noninvasively using a novel technique based on Compton scattering effect. The density of the cancellous and cortical bone was decreased in nine and six patients, respectively. During a follow-up period of up to 19 months, a further significant decrease in the density of both bone components was found. We conclude that prolonged HTPN is associated with an ongoing bone diminution, affecting mainly the cancellous bone.

Zinc excretion in osteoporotic women.

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)

Effect of swimming on bone growth and development in young rats.

The effect of chronic swimming on bone modelling was studied. Forty female Sabra rats (5 weeks old) were randomly assigned to the following experimental groups: 30 rats were trained to swim (water bath 35 +/- 1 degree C, one h daily, five times a week) for 20 weeks--20 of them loaded with lead weights (1% body weight) while the rest (10 animals) swam load free. Ten sedentary rats matched for age and weight served as controls. At the end of the twenty-week swimming period, all rats were sacrificed, both humeri bones were dissected and prepared for the following examinations: morphometric, bone density (BD), bone mineral content (BMC), compression tests and cross-sectional geometrical parameters, histomorphometry and biochemical analysis of minerals (Ca, Pi, Mg, Zn). All measured parameters were found to be significantly higher (P less than 0.05) in the swimming rats irrespective of load, as compared with the controls. Bone weight was higher by 19%, bone volume by 11%, bone length by 2.8%, cortical area by 16%, BD by 7% and BMC by 15%. The compression breaking force at the distal shaft of the humerus was higher by 24% in the trained group, while the ultimate compressive stress was not significantly different. Maximal and minimal moment of inertia at the distal diaphysis were 33.4 and 40% higher, respectively, for the swimming groups than the controls. Ca, Pi, Mg and Zn levels per total humeral bone were significantly higher in the exercising rats. The histomorphometry and cross-sectional data emphasize longitudinal and transversal growth. These data indicate that swimming exercise exerts a positive effect on bone growth and development in young rats.

Osteogenic response to marrow aspiration: increased serum osteocalcin and alkaline phosphatase in human bone marrow donors.

It has been shown recently in experimental animals that regeneration of bone marrow after ablation is associated with enhanced osteogenic growth factor activity and a systemic increase in bone formation. To assess the possible occurrence of a similar phenomenon in humans, serum markers of bone formation, osteocalcin and alkaline phosphatase, were measured in marrow donors before the aspiration of large amounts of iliac marrow and 1 day to 5 weeks thereafter. Both osteocalcin and alkaline phosphatase showed significant increases, with peak values 1-3 and 2-4 weeks postaspiration, respectively. The absolute maximal increase in osteocalcin was significantly higher in adolescent and child donors than in adults. When evaluated together with studies on systemic changes during fracture healing and marrow regeneration, these findings suggest that marrow aspiration in humans evokes a systemic osteogenic response.

Vitamin D in Paget's disease of bone.

The role of vitamin D metabolism in Paget's disease of bone has not been well defined. Serum levels of the main, circulating vitamin D metabolites were measured in 23 patients with Paget's disease. Values of 25(OH)D3 and 24,25(OH)2D3 were within the normal range in most (more than 90%) of the subjects. 1,25(OH)2D3 was increased in 11 (48%) patients. Markedly elevated levels (93-298 pg/ml) were found in five patients. In a subgroup of patients with high 1,25(OH)2D3, the mean serum alkaline phosphatase activity was insignificantly higher, while serum calcium, phosphorous, and kidney function were the same as in a subgroup with normal 1,25(OH)2D3. 1,25(OH)2D3 levels were not affected by treatment with either calcitonin or etidronate disodium. Serum 1,25(OH)2D3 levels may be increased in a subset of patients with Paget's disease of bone.

Studies of normal and prematurely ruptured human amniotic membranes: low calcium and magnesium in prematurely ruptured membranes.

Prematurely ruptured amniotic membranes at term, and membranes from normal term pregnancies were studied. The membranes were analyzed for neutral sugars, hexosamines, sialic acid, uronic acid, DNA, RNA, cholesterol, phospholipids, calcium, magnesium, sodium and potassium. The only significant difference found between the normal and the prematurely ruptured membranes was a significantly lower concentration of calcium and magnesium in the latter group. (Calcium 0.32 +/- 0.07, vs. 0.24 +/- 0.07, p less than 0.05; Magnesium 0.30 +/- 0.19 vs. 0.15 +/- 0.04, p less than 0.05; in mg/100 mg protein). The possible metabolic effects of low calcium and magnesium may be of relevance to the pathogenesis of premature rupture of the amniotic membranes.

Erythrocyte hexose monophosphate shunt is intact in healthy aged humans.

The integrity of the erythrocyte (RBC) hexose monophosphate shunt was investigated in a group of 33 healthy elderly individuals by determining their RBC glutathione content, glucose-6-phosphate dehydrogenase activity and glutathione regeneration. When these parameters were compared with those of the controls, 44 young healthy adults, no significant differences were found. This study indicates that the RBC hexose monophosphate shunt in healthy elderly individuals is intact. Factors other than senescence per se should be sought in elderly individuals who exhibit dysfunction of this shunt.

Medical treatment of primary hyperparathyroidism: effects on parathormone and vitamin D metabolites.

A 63-year-old woman was treated medically for primary hyperparathyroidism because of a recent myocardial infarction. She received propranolol alone or combined with either cimetidine, calcitonin or disodium etidronate (EHDP). The treatment did not affect the elevated serum parathormone or urinary cyclic AMP levels, nor did it correct the elevated serum 1,25(OH)2D and the decreased serum 24,25(OH)2D levels in this patient. Propranolol combined with either cimetidine or with EHDP (600 mg/day) caused a mild decrease in the serum calcium level which, however, remained within the hypercalcemic range. Following surgery all parameters returned to normal. We conclude that the above medical regimens were incapable of correcting the hyperparathyroid condition in this patient.

An investigation of calcium intake, 1-alpha(OH)D3, and etidronate on bone.

The synthetic metabolite of vitamin D3 [1 alpha(OH)D3] caused a significant plasma calcium elevation in rats only when dietary calcium was low. Animals given the low calcium diet (0.005%) had lower plasma parathyroid hormone (PTH) levels when the diet contained 1 alpha(OH)D3 and significantly higher levels than animals on a high calcium (0.95%) diet, with or without the vitamin. The nutritional stress of a low calcium diet without 1 alpha(OH)D3 resulted in a prolonged severe hypocalcemia and elevated serum PTH levels. A higher ash, phosphate, and calcium content was found in the bones of animals fed the high calcium diet, with no vitamin D3 that were given etidronate (EHDP). When animals received the same calcium diet with 1 alpha(OH)D3 supplementation, EHDP administration increased the percentage of bone ash but had no effect on ash weight. 1 alpha(OH)D3 or EHDP did not affect ash weight, dry fat free weight, and percentage of ash of bone of animals receiving a low calcium diet. The percentage of calcium and phosphorus in bone ash was similar among all groups, although the amounts per humerus were characteristically related to the calcium intake. There was approximately 20-25% less bone mineral and calcium and phosphorus in the humeri of low calcium intake animals than in animals provided an adequate dietary calcium.