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PubMedDate not supplied

Vitamin d-receptor gene polymorphisms and vertebral bone density in men with idiopathic hypogonadotrophic hypogonadism.

BACKGROUND: Optimal peak bone mass is closely related to sufficient and appropriately timed androgen release. However, attainment of peak bone mass in men, as in women, is under genetic control, as well as being subject to hormonal and mutational effects. With increasing recognition of osteoporosis and related fractures in men, it is of interest to consider whether there is relationship between bone density and vitamin D receptor (VDR) polymorphisms, as described in women. MATERIAL AND METHODS: To assess the influence of allelic variation in the VDR gene on vertebral bone density in men with idiopathic hypogonadrotrophic hypogonadism (IHH), 27 patients (mean age 21.4 +/- 0.4 yrs) and 25 age-and-BMI matched healthy males (mean age 21.2 +/- 0.3) were genotyped using three restriction enzymes (Apa I, Bsm I, and Taq I). Vertebral bone mineral density was measured using dual energy X-ray absorptiometry (DEXA). RESULTS: As expected, vertebral bone density was reduced significantly in patients with IHH (p < 0.001). Despite weak evidence for an association between Apa I polymorphism and vertebral bone density in the IHH group (r = 0.454, p = 0.017 and r2 = 0.20), VDR genotype was not associated with vertebral bone density in either group. When analyzing homozygous haplotypes, the probability of carrying the favorable BAt haplotype was greater in the control group (OR = 2.000 vs. 0.500). CONCLUSION: We conclude that VDR genotype has no influence on vertebral bone density in men with IHH. Thus, allelic variation in the VDR cannot help define those at increased risk for osteoporosis and related fractures among such patients.

Absorptiometry, Photon↗

PubMed1999

Bone density, vitamin D status, and disordered bone remodeling in end-stage chronic liver disease.

Hepatic osteodystrophy occurs in up to 50% of patients with chronic liver disease (CLD). The aim of this study was to determine the relative contribution of increased resorption and decreased formation to hepatic osteodystrophy by measuring biochemical markers. Twenty-seven patients with advanced CLD (14 female, 13 male) were enrolled. Bone mineral density (BMD), measured at the lumbar spine, and femoral neck, were measured by dual energy X-ray absorptiometry (DXA); bone turnover was assessed using biochemical markers of bone formation and resorption. Based on WHO criteria, osteoporosis and osteopenia were present in 41% and 18% of patients, respectively. All three markers of bone resorption (free deoxypyridinoline, pyridinoline, and hydroxyproline) were increased significantly in patients with CLD. There was a less marked change in the markers of bone formation (osteocalcin, procollagen type 1 peptide, and bone alkaline phosphatase), resulting in a negative uncoupling index in 23/27 (85%) of the patients. Only two (7%) patients had biochemical changes consistent with osteomalacia. The results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and therapeutic strategies should be designed to suppress bone resorption, especially in preparation for liver transplantation. Bone biomarkers may be useful alternatives to bone biopsy in evaluating hepatic osteodystrophy.

Absorptiometry, Photon↗

PubMed1992

[Idiopathic hypercalciuria and bone density].

A decrease in bone density of the spine has been reported in individuals with hypercalciuria and the finding of the latter in osteoporosis patients is not uncommon. We studied 21 men and 8 women (mean age 47 +/- 13) with idiopathic hypercalciuria (IHCU) defined by an urinary calcium of more than 7.5 mmol/24 h in men and 6.25 mmol/24 h in women. The duration of IHCU was 10 (+/-) 8 years. Among the 29 patients, 24 had one or more renal calculi. Twenty one had been treated, by low calcium diet only (and diuresis), combined with a thiazide diuretic, or sodium phytate, or phosphorus. Bone mineral content (BMC) was measured in the lumbar spine and the upper end of the femur using an ORIS ODC 200 densitometer and compared with 29 control subjects paired for age and sex. No difference was found between the two groups concerning BMC values in either the spine or the 3 femoral sites (neck, Ward, trochanter). BMC was not correlated with urinary calcium. Thus individuals with IHCU showed no decrease in their bone mass, among this group seen in a department of nephrology. The influence of the treatment of IHCU remains to be defined.

Adult↗

PubMed1999

Bone density in human dentate and edentulous mandibles using computed tomography.

Mandibular bone density, vertebral density and resorption of the edentulous ridge were correlated in a group of 17 partially edentulous subjects. Bone density was quantified by Quantitative Computerized Tomography; resorption was evaluated on panoramic radiographs. Mean bone density in dentate areas was significantly higher than that in edentulous areas; mandibular bone density was not found to relate significantly to vertebral bone density, nor to ridge resorption. In programming osseointegrated implants in the partially edentulous mandible, CT may give a more accurate evaluation of trabecular bone. However, further studies are necessary to clarify its clinical utility.

Adult↗

PubMed2006

Effectiveness of bone density measurement for predicting osteoporotic fractures in clinical practice.

CONTEXT: Bone density measurement with dual-energy x-ray absorptiometry is widely used for fracture risk assessment. It has not been established that published gradients of fracture risk from study populations can be directly applied to clinical populations. OBJECTIVE: The objective of the study was to assess osteoporotic fracture prediction with dual-energy x-ray absorptiometry in a large clinical cohort. DESIGN: This was a historical cohort study (mean observation period 3.2 +/- 1.5 yr). PATIENTS: The study population was drawn from the population-based database of the Manitoba Bone Density Program. Analyses were limited to women aged 50 yr or older at baseline (n = 16,505). MAIN OUTCOME MEASURE: Each subject's longitudinal health service record was assessed for the presence of nontrauma fracture codes (hip, spine, wrist, and humerus) after bone density testing. Age-adjusted hazard ratios for fracture were derived from Cox proportional hazards models. RESULTS: Site-specific and overall fracture rates were significantly associated with each site of bone density measurement (all P < 0.00001). The 95% confidence intervals overlapped those from a widely cited metaanalysis of fracture prediction from different sites. Although fracture prediction was not significantly different between the three hip measurement sites, each hip site was better than the lumbar spine for predicting overall fractures (nonoverlapping 95% confidence intervals). The manufacturer sd (equivalent to a unit change in T-score) resulted in a significantly smaller gradient of risk for the spine than when the population sd was used. CONCLUSIONS: Bone density measurements are effective for predicting fractures in clinical practice. However, hip measurements were superior to the spine in overall osteoporotic fracture prediction.

Absorptiometry, Photon↗

PubMed2003

Gender differences in volumetric bone density: a study of opposite-sex twins.

Gender difference in bone size is a potential confounder when comparing bone density between males and females. A comparison of volumetric BMD (vBMD) between men and women, which is a measure of bone mass relative to three-dimensional bone volume (g/cm(3)) as opposed to areal bone density (g/cm(2)), may be a more accurate reflection of gender differences in bone density. The aims of this study were to examine gender differences in bone mass (BMC), areal BMD (aBMD), volumetric BMD (vBMD) by comparing twins of opposite sex in whom the effects of age, genes and environment are partially controlled for. DEXA derived BMC, aBMD, vBMD at the third lumbar vertebra (L3), femoral neck (FN) and forearm (1/3 radius) were compared between 82 opposite sex pairs aged 18-80. BMC was significantly higher in males at all three sites (26-45.5%). For aBMD the gender differences remained significant at all sites except the spine. The average differences in aBMD were not as great as the differences in BMC (2.2-20.5%). The differences in vBMD, however, followed a different pattern. FN and L3 vBMD were significantly higher in females (4.8 and 0.6%, respectively), while radial BMD was not significantly different between the sexes. Comparing aBMD values between males and females, when females in general have a smaller skeleton than males may not be a true indication of gender differences in bone density. A comparison of vBMD between men and women shows only small differences in bone density between the sexes.

Adult↗

PubMed2004

Effects of risedronate on bone density in anorexia nervosa.

Anorexia nervosa (AN), a psychiatric disease characterized by chronic starvation, is complicated by severe bone loss (1), for which there is no effective, available therapy. Although bone resorption is markedly increased in these patients, estrogen is an ineffective anti-resorptive therapy in the setting of undernutrition. We hypothesized bisphosphonate administration would result in a decrease in bone resorption and an increase in bone density in women with AN and bone loss, despite undernutrition. We therefore administered risedronate 5 mg daily for nine months to 10 women with AN, all of whom had osteopenia (mean AP spine T score: -2.7 +/- 2) and compared NTX and bone density with baseline values and with those from available control data prospectively followed for the same time period. Bone density increased significantly in patients who received risedronate compared with controls and compared with baseline, despite lack of significant weight gain, for an increase of AP spine bone density of 4.1 +/- 1.6% at six months and 4.9 +/- 1.0% at nine months. Bone resorption, as measured by NTX, decreased 23.8% at one month and 29.6% at three months, from the high-normal to mid-normal range of young women. Our data suggest that risedronate 5 mg daily administered to women with AN and osteopenia may increase in bone density at the AP spine despite low weight. This is the first study to demonstrate marked increases in bone density in women with AN. Because of the lack of data regarding the safety of such medications in women of reproductive age, bisphosphonates are not approved in the U.S. for premenopausal women other than those receiving glucocorticoids. Further studies are needed to establish the efficacy and safety of bisphosphonate therapy in this population.

Adult↗

PubMed1995

A longitudinal study of the effect of spinal degenerative disease on bone density in the elderly.

OBJECTIVE: To describe the relationship between spinal degenerative disease and bone density in the elderly both cross sectionally and longitudinally. METHODS: Random population based sample of 113 men and 187 women over 60 yrs of age participating in the Dubbo Osteoporosis Epidemiology Study (a longitudinal population based study of fracture risk factors) who had bone density measured on 2 occasions (average interval 2.5 yrs) and spinal radiographs on one occasion (performed according to a standardized approach). RESULTS: Spinal degenerative disease, of varying severity, was common in this population (osteophytes 69%, disc narrowing 67%, posterior element disease 99%). Scores for osteophytosis, disc narrowing, and posterior element disease (together with age and body mass index) independently explained 43% of the variation in spinal bone density in men (p < 0.00001) and 26% in women (p < 0.00001). The rate of change at the spine increased with increasing severity of osteophytosis in both men (p = 0.03) and women (p = 0.05), but not the other measures, and the total amount of variation explained by these measures was modest. In comparison, severity of spinal degenerative disease had only a modest but significant relationship with femoral neck bone density in both sexes, but not its rate of change. Subjects with any degree of osteophytosis had higher bone density compared to those without osteophytes at both the lumbar spine (men 21% higher, 95% CI 12-31; women 16% higher, 95% CI 9-23) and, to a lesser extent, femoral neck (men 12% higher, 95% CI 4-20; women 6% higher, 95% CI 1-13). Vascular calcification had no relationship with bone density at either spine or hip. CONCLUSION: Spinal bone density measurement and its sequential followup may be erroneous in the elderly due to concomitant degenerative disease. Bone density at the femoral neck was much less affected by spinal degenerative disease, which suggests that this site may be more efficacious for both monitoring response to treatment and determining fracture risk in the elderly.

Absorptiometry, Photon↗

PubMed1991

Bone density measurements.

Early diagnosis of osteoporosis is difficult. Bone density measurements, however, are helpful in screening patients at risk. Technology now provides means of measuring densities of both peripheral and central bones. The most practical method is dual X-ray densitometry, which is of good sensitivity and accuracy. Single photon absorptiometry on peripheral bones can be used to screen populations at risk. Computed tomography is also useful but the radiation dose is relatively high. In dual X-ray densitometry, calibration methods and comparisons with reference values are fairly reliable. The best sites for measurements are the lumbar spine and proximal femur, in which osteoporotic fractures are common. In general, however, one measurement is not enough. Biological variation is great. Repeated measurements will allow estimation of the rate of bone loss. Precise location of a previous site is sometimes difficult on reexamination and extraskeletal calcifications can be sources of error. Bone densitometry in connection with the prevention and treatment of osteoporosis is fairly easily performed with a single patient. Knowledge about the correlation between bone density and fracture risk is not yet adequate. The results of measurement of bone mineral density relate only to mineral content, not bone quality, i.e., differential diagnosis of osteoporosis and osteomalacia is not possible.

Absorptiometry, Photon↗

PubMedDate not supplied

Determination of bone density by coherent-Compton scattering.

Bone density previously has been determined by counting the number of Compton and coherently scattered photons using incident radiation from 241Am (60 keV). We have improved this technique by using more nearly optimal scattering angles and a higher incident beam energy. Three factors make this method clinically attractive; (a) sensitivity to changes in both bone density and elemental composition, (b) elimination of attenuation corrections for overlaying structures, and (c) the ability to measure the axial skeleton. An intrinsic Ge detector with high resolution (500 eV at 100 keV) allowed measurement of forward scatter at angles as low as 30 degrees (from the incident beam), thereby maximizing the fluence of the coherent photons which are highly forward directed. Preliminary results showed high correlations (r = 0.97-0.99) between the coherent-Compton ratio and density of bone phantoms using both 241Am and 153Gd sources. The skin dose for a measurement using 153Gd was calculated to be 1.5 cGy at 3% counting precision.

Americium↗

PubMed1993

Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group.

Women with low bone density in the radius or calcaneus are at increased risk of hip fracture. To see whether bone density of the hip measured by dual X-ray absorptiometry is a better predictor of hip fracture than measurements of other bones, we assessed bone density at several sites in 8134 women aged 65 years or more. 65 women had hip fractures during a mean follow-up of 1.8 years. Each SD decrease in femoral neck bone density increased the age-adjusted risk of hip fracture 2.6 times (95% CL 1.9, 3.6). Women with bone density in the lowest quartile had an 8.5-fold greater risk of hip fracture than those in the highest quartile. Bone density of the femoral neck was a better predictor than measurements of the spine (p < 0.0001), radius (p < 0.002), and moderately better than the calcaneus (p = 0.10). Low hip bone density is a stronger predictor of hip fracture than bone density at other sites. Efforts to prevent hip fractures should focus on women with low hip bone density.

Absorptiometry, Photon↗

PubMed1993

Bone density in old chickens' metaphyses, as affected by local trauma and chondrocyte implantation.

Resurfacing of joints by chondrocyte implants often leads to an increased subchondral bone density. To further evaluate this phenomenon, this study analyzed bone density and bone formation in three groups of 3-year-old chickens (90 animals, 30 per group): (1) implantation of chondrocytes embedded in hyaluronic acid (HA) into the tibial metaphysis; (2) implantation of delivery substance only; (3) sham-operated control group. Results were assessed biochemically, histologically, and histomorphometrically at 6 weeks and 6 months postimplantation. A 1.5-fold increase in the metaphyseal bone density was observed in the HA-implanted controls, as compared to sham-operated/normal joints. A further increase in bone density to twice the density of the sham-operated joints was achieved by implantation of chondrocytes. In bones implanted with cells, long-lasting (6 weeks) cartilage nodules were observed, which eventually underwent hypertrophy. The implanted chondrocytes were surrounded by a dense inflammatory infiltrate, which did not prevent the induction and formation of new bone. Based on these findings, it was concluded that chondrocyte implantation into bones results in an increase in local bone density due to a prolonged process of endochondral ossification. Further studies are necessary to evaluate the possible application of this implantation procedure in osteoporosis.

Animals↗

PubMed1993

Importance of bone resorption in the determination of bone density in women more than 10 years past the menopause.

There is general agreement that bone density falls with age and is higher in heavy people than light people. We have studied a variety of potential correlates of vertebral, ankle, and hip bone density to evaluate other potential influences on the skeleton. We recruited 196 healthy women who were more than 10 years past the menopause and collected a diet and activity record, a 24 h urine, and a fasting blood and urine specimen. These blood and urine samples were analyzed for factors related to calcium homeostasis. We then measured bone density at lumbar vertebrae 1-4 and the hip and the ankle bone density of the nondominant leg. Correlations between vertebral, hip, and ankle bone density and other measured variables were explored using the statistical package SPSS PC. At the vertebral site, in addition to correlations with age and body mass index (BMI), a negative correlation with a measure of bone resorption, the hydroxyproline creatinine ratio (OHPCR), was noted. At the ankle site, in addition to correlation with age, BMI, and OHPCR, a positive correlation with activity and a negative correlation with serum calcitriol were noted. At the hip site, as well as age, BMI, and OHPCR, significant correlations with GFR and dietary calcium intake were noted. These data suggest that even in women 10 years past the menopause bone resorption has a significant effect on bone density, that renal function may account for some of the variance in bone density at the hip, and that activity effects are more marked at sites of greater loading, namely the ankle.

Aged↗

PubMed1988

Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women.

The effect of long-term L-thyroxine (L-T4) therapy on axial skeleton bone density was studied in 31 premenopausal women; the bone densities of these women were compared with the bone densities of 31 age- and weight-matched women without thyroid or bone abnormalities. The women receiving L-T4 therapy had been receiving the medication for a minimum of five years. There was no difference in calcium intake or excretion between the L-T4-treated women and the controls. Women receiving L-T4 had increased serum thyroxine concentrations (134 +/- 5 vs 95 +/- 3 nmol/L [10.4 +/- 0.4 vs 7.4 +/- 0.2 micrograms/dL]), an increased free thyroxine index (9.4 +/- 0.4 vs 6.8 +/- 0.2), and decreased serum thyroid-stimulating hormone concentrations (0.9 +/- 0.2 mU/L vs 2.1 +/- 0.3 mU/L [0.9 +/- 0.2 vs 2.1 +/- 0.3 microU/mL]). Serum triiodothyronine concentrations were normal and were similar in both groups. Women treated with L-T4 had a 12.8% lower bone density at the femoral neck and a 10.1% lower bone density at the femoral trochanter compared with matched controls. In contrast, lumbar spine bone density was similar in the two groups. The data suggest that long-term L-T4 therapy, which is often given at supraphysiologic dosages, may predispose patients to decreased bone density in the hip and may increase the risk of age-related bone loss. It is advisable, therefore, to employ a dosage of L-T4 that is carefully monitored to avoid the long-term use of dosages that are excessive for the thyroid condition being treated.

Adult↗

PubMed1985

Correlates of mid-radius bone density among postmenopausal women: a community study.

We surveyed mid-radius bone density in a geographically-defined population of 324 women, 55-80 years old from two small, demographically-similar communities whose water supply provided 60 mg/l and 375 mg/l of elemental calcium. Mean community calcium intakes were 964 mg/day and 1329 mg/day respectively. Bone density, measured by photon densitometry, was correlated with physical measurements, medical history, and reported nutritional intake. Mid-radius bone density decreased with age while the following additional factors were independently and positively associated with bone density: humeral muscle area (p = 0.0001), extended estrogen use (p = 0.0004), thiazide use (p = 0.0029), and vitamin D intake (p = 0.0104). Estimated total calcium intake alone did not significantly correlate with bone density; however, mean bone density was significantly greater in persons whose calcium intake was greater than 800 mg/day, consumed concurrently with vitamin D in amounts greater than 400 IU (p = 0.0342), the Recommended Daily Allowance of these two nutrients.

Aged↗

PubMedDate not supplied

Relationship between articular cartilage damage and bone density in the first metatarsal.

It is well known that bone changes occur in relationship to the articular cartilage damage seen in osteoarthritis. Numerous studies have shown a relationship between bone density and articular cartilage damage in knee and hip joints, but it is controversial as to whether or not an increased subchondral bone density results in greater cartilage damage. We studied 49 pairs of cadaveric first metatarsals in an attempt to correlate the level of cartilage damage seen on the distal articular surface with areal and volumetric density and other parameters such as bone geometry. A positive correlation was detected between articular cartilage damage and bone density by peripheral quantitative computed tomography in five of eight frontal slices in the head of the left metatarsal in the male sample only. The more extensive subchondral cysts found in the right male metatarsal may have contributed to the lack of correlation between the two variables on the right side. In addition, females displayed significantly greater osteophytosis than males at a given grade of cartilage damage, thus, possibly leading to a painful, apropulsive gait and a disuse osteopenia which would neutralize any subchondral bone density increase associated with cartilage damage. Microscopic investigations are, therefore, warranted to detect bone changes on a more discreet level, particularly within the subchondral plate.

Adult↗

PubMed1994

Cyclic medroxyprogesterone treatment increases bone density: a controlled trial in active women with menstrual cycle disturbances.

OBJECTIVE: Bone loss occurs in young women who experience amenorrhea or ovulatory disturbances. The purpose of this study was to determine whether bone loss could be prevented by simulating a more normal hormonal pattern, using treatment with cyclic medroxyprogesterone, with or without calcium supplementation, in physically active women with disturbed menstruation. DESIGN: This study was a 1-year randomized, double-blind, placebo-controlled trial. Women who were stratified by menstrual cycle disturbance were randomized into four groups. The outcome variable was the change in spinal bone density measured by dual energy techniques. SETTING: A large metropolitan area. PARTICIPANTS: Sixty-one healthy, normal-weight physically active premenopausal women aged 21 to 45 years who experienced amenorrhea, oligomenorrhea, anovulation, or short luteal phase cycles completed the study. INTERVENTION: Therapies were cyclic medroxyprogesterone (10 mg/day for 10 days per month) and calcium carbonate (1,000 mg/day of calcium) in four groups: (A) (n = 16) cyclic medroxyprogesterone plus calcium carbonate; (B) (n = 16) cyclic medroxyprogesterone with calcium placebo; (C) (n = 15) placebo medroxyprogesterone with active calcium; or (D) (n = 14) both medroxyprogesterone and calcium placebos. RESULTS: The initial bone density (mean = 1.12 g/cm2) did not differ by group (P = 0.85). The 1-year bone density change was strongly related to treatment with medroxyprogesterone (P = 0.0001) and weakly to calcium (P = 0.072) treatment. Bone density increased significantly (+1.7% +/- 0.5%, +/- SEM, P = 0.004) in the medroxyprogesterone-treated groups (A and B), did not change in the calcium-treated group (C) (-0.7% +/- 0.6%, P = 0.28), and decreased on both placebos (D) (-2.0% +/- 0.6%, P = 0.005). CONCLUSIONS: Cyclic medroxyprogesterone increased spinal bone density in physically active women experiencing amenorrhea or ovulatory disturbances. POTENTIAL CLINICAL SIGNIFICANCE: Amenorrhea, oligomenorrhea, anovulation, and short luteal phase cycles are common in premenopausal women and associated with spinal bone loss occurring at a stage of life when bone density would normally be stable or increasing. This controlled trial shows a significant gain in bone in women in the cyclic medroxyprogesterone intervention group, whereas those subjects in the placebo group lost bone. Calcium supplementation appeared to be helpful but did not reach statistical significance. The implications of these findings for the prevention of osteoporosis warrant further investigation.

Adult↗

PubMed1987

Adrenal androgens, sex-hormone binding globulin and bone density in osteoporotic menopausal women: is there a relationship?

The relationships among sex steroids, sex hormone binding globulin (SHBG) and vertebral bone density as measured by computerized tomography were studied in 18 post-menopausal women. A significant negative correlation was found between SHBG binding capacity (SHBG-BC) and bone density. Bone density and the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) declined with age, and SHBG-BC was correlated significantly with DHEAS concentrations. The relationship between SHBG-BC and bone density may be affected by adrenal androgen output.

Adrenal Cortex Hormones↗