Effects of nitric oxide synthase gene knockout on neurotransmitter release in vivo

Previous studies suggest that low bone mass is a complication of alcoholic liver disease. Nevertheless, little is known about bone mass and bone metabolism in viral cirrhosis. To evaluate the prevalence and magnitude of hepatic osteopenia in these patients, bone remodeling status, and its relationship with the severity of liver disease and serum levels of insulin-like growth factor I (IGF-I), we studied 32 consecutive patients with viral cirrhosis and no history of alcohol intake. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN), and the values were expressed as the z score. Bone metabolism markers and hormone profiles were measured. Patients with viral cirrhosis showed reduced BMD in all sites (LS: -1.27 +/- 1.06, P < .001; FN: -0.48 +/- 0.96; P < .01). Of the 32 patients, 53% met the diagnostic criteria for osteoporosis. In patients, urine deoxypyridinoline (D-Pyr) as a marker of bone resorption and serum bone alkaline phosphatase (b-AP) as a marker of bone formation were significantly higher than in control subjects (P < .001 and P < .01, respectively). Serum IGF-I was lower than in control subjects (P < .001), and significant differences were also found between patients with and without osteoporosis (P < .05). BMD in LS correlated with severity of the disease, with serum levels of IGF-I, and with urine D-Pyr. Our findings show that viral cirrhosis is a major cause of osteoporosis in men, and that low serum IGF-I levels seem to play a role in the bone mass loss in these patients. The biochemical markers of bone remodeling suggest high-turnover osteoporosis in patients with viral cirrhosis.     

Decreased bone mineral density in premenopausal patients with systemic lupus erythematosus

To study bone mineral density (BMD) in premenopausal adult female patients with systemic lupus erythematosus (SLE) and its relation with clinical parameters, 56 SLE patients (mean age 31 years, mean disease duration 6.3 years) and 15 normal controls were studied. BMD at the lumbar vertebrae (L2-L4) was measured by dual energy X-ray absorptiometry (DEXA). Classification of BMD was made according to the WHO criteria in 1994. Correlation between BMD and clinical parameters was calculated. It was found BMD in the SLE patients (0.942 +/- 0.136 g/cm2) was lower than in the control group (1.055 +/- 0.080 g/cm2) (P < 0.01). According to the WHO criteria, 17 patients (30%) had normal BMD, 22 patients (40%) had osteopenia and 17 patients (30%) had osteoporosis. BMD was inversely correlated with disease duration in SLE patients (p < 0.005). The minimal disease duration for a female SLE patient to develop osteopenia was 3.5 years. In conclusion, SLE patients have lower lumbar BMD than normal controls. SLE patients with longer disease duration have lower BMD. In order to achieve early prevention of osteoporosis, we suggest that female SLE patients with disease duration for more than 3.5 years should take a BMD examination.     

Effects of growth hormone (GH) replacement on bone metabolism and mineral density in adult onset of GH deficiency: results of a double-blind placebo-controlled study with open follow-up

It is known that GH stimulates bone turnover and that GH-deficient adults have a lower bone mass than healthy controls. In order to evaluate the influences of GH replacement therapy on markers of bone turnover and on bone mineral density (BMD) in patients with adult onset GH deficiency, a double-blind placebo-controlled study of treatment with recombinant human GH (rhGH; mean dose 2.4 IU daily) in 20 patients for 6 months and an extended open study of 6 to 12 months were conducted. Eighteen patients, fourteen men and four women, with a mean age of 44 years with adult onset GH deficiency were evaluated in the study. Compared with placebo, after 6 months serum calcium (2.39 +/- 0.02 vs 2.32 +/- 0.02 mmol/l, P = 0.037) and phosphate (0.97 +/- 0.06 vs 0.75 +/- 0.05 mmol/l, P = 0.011) increased and the index of phosphate excretion (0.03 +/- 0.03 vs 0.19 +/- 0.02, P < 0.001) decreased significantly, and there was a significant increase in the markers of bone formation (osteocalcin, 64.8 +/- 11.8 vs 17.4 +/- 1.8 ng/ml, P < 0.001; procollagen type I carboxyterminal propeptide (PICP), 195.3 +/- 26.4 vs 124.0 +/- 15.5 ng/ml, P = 0.026) as well as those of bone resorption (type I collagen carboxyterminal telopeptide (ICTP), 8.9 +/- 1.2 vs 3.3 +/- 0.5 ng/ml, P < 0.001; urinary hydroxyproline, 0.035 +/- 0.006 vs 0.018 +/- 0.002 mg/100 ml glomerular filtration rate, P = 0.009). BMD did not change during this period of time. IGF-I was significantly higher in treated patients (306 +/- 45.3 vs 88.7 +/- 22.5 ng/ml, P < 0.001). An analysis of the data compiled from 18 patients treated with rhGH for 12 months revealed similar significant increases in serum calcium and phosphate, and the markers of bone turnover (osteocalcin, PICP, ICTP, urinary hydroxyproline). Dual energy x-ray absorptiometry (DXA)-measured BMD in the lumbar spine (1.194 +/- 0.058 vs 1.133 +/- 0.046 g/cm2, P = 0.015), femoral neck (1.009 +/- 0.051 vs 0.936 +/- 0.034 g/cm2, P = 0.004), Ward's triangle (0.881 +/- 0.055 vs 0.816 +/- 0.04 g/cm2, P = 0.019) and the trochanteric region (0.869 +/- 0.046 vs 0.801 +/- 0.033 g/cm2, P = 0.005) increased significantly linearly (compared with the individual baseline values). At 12 months, BMD in patients with low bone mass (T-score < -1.0 S.D.) increased more than in those with normal bone mass (lumbar spine 11.5 vs 2.1%, P = 0.030, and femoral neck 9.7 vs 4.2%, P = 0.055). IGF-I increased significantly in all treated patients. In conclusion, treatment of GH-deficient adults with rhGH increases bone turnover for at least 12 months. BMD in the lumbar spine and the proximal femur increases continuously in this time (open study) and the benefit is greater in patients with low bone mass. Therefore, GH-deficient patients exhibiting osteopenia or osteoporosis should be considered candidates for GH supplementation. However, long-term studies are needed to establish that the positive effects on BMD are persistent and are associated with a reduction in fracture risk.     

Revision of the nomenclature for the Bacillus thuringiensis pesticidal crystal proteins

The aim of this prospective study was to evaluate the bone mineral density (BMD) at lumbar spine and femoral neck levels and biochemical parameters of bone turnover in 20 consecutive hyperprolactinemic males before and after an 18-month treatment with different dopamine agonists. Six patients received bromocriptine at a dose of 2.5-10 mg/day; 7 patients received quinagolide at a dose of 0.075-0.3 mg/day; 7 patients received cabergoline at a dose of 0.5-1.5 mg/week. BMD, serum PRL, testosterone, dihydrotestosterone, and osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured before and every 6 months during treatment. At study entry, BMD values were lower in patients than controls at both lumbar spine (0.82 +/- 0.03 vs. 1.18 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.85 +/- 0.02 vs. 0.92 +/- 0.02 g/cm2; P < 0.05) levels. Osteopenia or osteoporosis was diagnosed in 16 patients at the lumbar spine and in 6 of them at the femoral neck level. A significant inverse correlation was found between lumbar spine and femoral neck BMD values and both PRL levels and disease duration (P < 0.01). In the 20 patients, serum OC levels were significantly lower (2.1 +/- 0.1 vs. 9.3 +/- 2.4 microg/L; P < 0.01), whereas Ntx levels were significantly higher (157.8 +/- 1.1 vs. 96.4 +/- 7.4 nmol bone collagen equivalent/mmol creatinine; P < 0.001) than control values. A significant inverse correlation was found between serum PRL and OC (P < 0.01), but not Ntx, levels. After 18 months of treatment, serum PRL levels were suppressed, and gonadal function was restored in all 20 patients, as shown by the normalization of serum T (from 2.2 +/- 0.2 to 5.0 +/- 0.2 microg/L) and dihydrotestosterone (0.3 +/- 0.02 vs. 0.5 +/- 0.01 nmol/L) levels, without any significant difference among groups. A progressive significant increase in serum OC levels together with a significant decrease in Ntx levels were observed after 6, 12, and 18 months of treatment in the 3 groups of patients. A slight, although significant, increase in BMD values was recorded in all patients after 18 months of bromocriptine, quinagolide, and cabergoline treatment, serum OC levels were normalized after treatment, whereas neither urinary Ntx levels nor BMD values were normalized by 18 months of treatment with dopaminergic agents. In conclusion, treatment with bromocriptine, quinagolide, and cabergoline for 18 months, although successfull in suppressing serum PRL levels and restoring gonadal function, was unable to restore lumbar spine and femoral neck BMD and normalize Ntx levels. However, BMD was slightly increased during treatment, suggesting that additional bone loss was prevented after treatment of hyperprolactinemia.     

Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.     

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63-89 years, mean +/- SD 76 +/- 7 years) and 162 age-matched female controls (age 62-90 years, mean +/- SD 75 +/- 7 years). BMD was measured in the femoral neck and lumbar spine (L2-4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504 +/- 0.097 v 0.597 +/- 0.101, p < 0.01, for femoral neck; 0.661 +/- 0.146 v 0.720 +/- 0.128, p < 0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm2 at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.     

Bone mass improves in alcoholics after 2 years of abstinence

To evaluate the effect of abstinence on bone mass and bone mineral metabolism in chronic alcoholics, a 2 year longitudinal follow-up study was carried out in a group of 30 chronic alcoholic males who started a rehabilitation program. Lumbar and femoral bone mineral density (BMD) and serum levels of osteocalcin and 25-hydroxyvitamin D were measured at entry and after 1 and 2 years in all patients. Circulating cortisol and parathyroid hormone were measured in 14 and 6 patients, respectively, at entry and every year. Testosterone was measured in 18 patients at entry and after 1 year. At entry, lumbar BMD was significantly lower in alcoholics (1.06 +/- 0.03 g/cm2) than in age-matched healthy men (1.22 +/- 0.03 g/cm2; p < 0.001). Circulating osteocalcin and vitamin D levels were also significantly lower in alcoholics than in controls. Lumbar and femoral neck BMD increased in alcoholics after 2 years of abstinence (lumbar BMD, mean +/- SEM, 1.06 +/- 0.03 to 1.10 +/- 0.04 g/cm2, p < 0.05; femoral BMD, 0.82 +/- 0.02 to 0.84 +/- 0.02 g/cm2; p < 0.02). Moreover, lumbar BMD increased in alcoholics (2.9 +/- 1.4%) and decreased in controls (-1.1 +/- 0.2%; p < 0.02). Femoral BMD also increased in alcoholics (2.8 +/- 1.0%) but the expected mean decrease of -0.92% was found in healthy age-matched males. Baseline low osteocalcin levels (5.1 +/- 0.6 ng/ml) increased after 1 year (8.6 +/- 0.5 ng/ml, p < 0.001) and 2 years of abstinence (9.5 +/- 0.7 ng/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of osteopenia and osteoporosis after kidney transplantation

BACKGROUND: Osteopenia and osteoporosis are frequent complications after kidney transplantation. Data for the treatment of low bone mass after kidney transplantation are not available. METHODS: To test the efficacy of antiresorptive treatment, 46 patients with osteopenia or osteoporosis after kidney transplantation (bone mineral density < or =1.5 SD below normal) were randomly assigned to three groups cyclically treated as follows: group 1 with daily oral clodronate (800 mg) and group 2 with daily intranasal calcitonin (200 IU) for 2 weeks every 3 months. These two groups were compared with a control group (group 3). Every patient was supplemented with 500 mg of calcium per day. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck before and after the 12-month treatment period. RESULTS: BMD at the lumbar spine was increased by 4.6% in the clodronate group (n=15, P=0.005), by 3.2% in the calcitonin group (n=16, P=0.034), and by 1.8% in the control group (n=15, P=0.265). However, the differences in BMD changes among the groups were not statistically significant. During therapy, serum calcium decreased slightly in all groups by 4.6%; however, parathyroid hormone values increased significantly in the treatment groups by 116%. Therapy was well tolerated without impact on graft function. CONCLUSIONS: Cyclical therapy with clodronate or calcitonin appears to induce a gain in BMD at the lumbar spine in patients with low bone mass after kidney transplantation. This treatment had no adverse impact on graft function but may aggravate preexisting secondary hyperparathyroidism.     

n-3 versus n-6 polyunsaturated fatty acids in critical illness

The aim of this study was to evaluate bone mineral density changes in patients with juvenile chronic arthritis (JCA) and to determine the most likely causes of osteoporosis in these patients. Eighteen (11 male, 7 female) patients suffering from JCA and 14 healthy controls (10 male, four female) were included in this study. The mean age of the patients and control groups were 11.0 +/- 3.2 and 10.9 +/- 2.9 years respectively. Disease activity was determined by clinical and laboratory evaluation and 'Articular Disease Severity Score' (ADSS). Bone mineral density (BMD) of the femoral neck and lumbar spine was measured by dual photon absorptiometry. BMD of the patients at the lumbar spine was significantly lower than the control group (p < 0.05). This difference was more marked in patients treated with steroids. Femoral neck BMD was also lower in the patient group but this difference was not statistically significant. There was a negative correlation between ADSS and BMD at the spine. In conclusion, trabecular bone loss is characteristic for osteoporosis in JCA. Our results indicate that steroid treatment and disease severity are important factors in the development of osteoporosis in JCA.     

Vitamin D and estrogen receptor allelic variants in Italian postmenopausal women: evidence of multiple gene contribution to bone mineral density

Bone mass and bone turnover are under genetic control. Restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus have been recently correlated to bone mineral density (BMD) and rate of bone loss. However, agreement on this relationship is not universal. The existence of ethnical and environmental differences between populations, a health-based selection bias in several previous studies, and the involvement of other genes could explain these discordant findings. In this study, we examined the relationship of VDR and estrogen receptor (ER) gene RFLPs with lumbar spine and upper femur BMD in 426 Italian postmenopausal women, 57.7 +/- 0.4 yr old (144 normal, 106 osteopenic, and 176 osteoporotic). VDR gene RFLPs for ApaI, Bsm I, and TaqI restriction endonucleases and ER RFLPs for PvuII and XbaI restriction endonucleases were assessed by Southern blotting analysis and were indicated, respectively, as A-a, B-b, T-t, P-p, and X-x (uppercase letters signifying the absence and lowercase letters the presence of the restriction site). After correcting for potential confounding factors (age, height, weight, age since menopause, osteophytosis, and facet joint osteoarthritis), a statistically significant VDR genotype effect on lumbar BMD (P = 0.01, analysis of covariance), but not on femoral BMD, was detected, with subjects in AABBtt genotype showing a 13% lower BMD than those with aabbTT genotype (P < 0.05, Tukey's test). Moreover, a statistically significant prevalence of AABBtt genotype in osteoporotics, and of AabbTT and aabbTT genotypes in nonosteoporotics, were detected. Conversely, there was no significant relationship of ER genotype to either lumbar or femoral BMD, even though a trend for higher BMD values in women with the ER PP genotype (with respect to those with ER pp genotype) was detected. When mean lumbar BMD was calculated for women grouped by ER and VDR genotype, we observed a significant difference between those within the 2 opposite associations AABBtt-PPXX and aabbTT-ppxx (0.71 +/- 0.05 vs. 0.97 +/- 0.03 g/cm2, P < 0.05 Tukey's test). These results are consistent with a segregation of the VDR AABBtt genotype with a higher risk of developing osteoporosis, in the Italian female population. The introduction of another variable, the ER genotype, in the analysis of VDR genetic determination of BMD, may represent a useful model in the identification of patients at risk of developing a multigenic disorder like osteoporosis.     

Does the vitamin D receptor genotype predict bone mineral loss in haemodialysed patients?

BACKGROUND: It has been suggested that the vitamin D receptor (VDR) gene BsmI-polymorphism is a genetic determinant of bone metabolism. DESIGN: To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 88 haemodialysed patients not receiving active vitamin D metabolites. METHODS: Whole body, lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1,25(OH)2D3, osteocalcin serum concentrations, alkaline phosphatase activity and intact 1,84 PTH levels were measured. RESULTS: VDR genotype BB, Bb and bb were found in 27, 49 and 24% of patients. Initial BMD (g/cm2) of whole body, lumbar spine and femoral neck did not differ between genotypes (whole body: BB 1.055 +/- 0.120, Bb 1.082 +/- 0.102, bb 1.128 +/- 0.120; lumbar spine: BB 1.075 +/- 0.199, Bb 1.079 +/- 0.185, bb 1.099 +/- 0.170; femoral neck: BB 0.808 +/- 0.160, Bb 0.862 +/- 0.127, bb 0.842 +/- 0.125; mean +/- SD), but the decrease of whole body and femoral neck BMD during 18 months was significantly (P < 0.02) different between the genotype groups (whole body: BB -0.048 +/- 0.028, Bb -0.031 +/- 0.029, bb -0.024 +/- 0.023; femoral neck BB -0.044 +/- 0.069, Bb -0.032 +/- 0.081, bb -0.012 +/- 0.029 g/cm2). CONCLUSION: This preliminary study suggests faster mineral loss in BB genotype of VDR in haemodialysed patients.     

Impetigo in French Guyana. A clinical, bacteriological, toxicological and sensitivity to antibiotics study]

Acromegalic patients present an increase of osteoblastic and osteoclastic activity, showing a different effect on the axial and appendicular skeletal structures. At this regard controversial data about bone mineral density (BMD) have been published in literature. In fact an increase of BMD levels in femoral neck and Ward's triangle without any difference in lumbar spine has been described. On the other hand normal BMD levels at forearm and reduced BMD levels at lumbar spine were found. These patients seem to have a reduction of trabecular BMD similar to postmenopausal osteoporotic patients despite normal or slightly elevated cortical BMD. Recently, it has been described that cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), are implicated in the pathogenetic mechanism of postmenopausal osteoporosis. Taking into account that growth hormone (GH) can increase TNF-alpha and IL-1 secretion by mononuclear blood cells, the evaluation of possible relationship between the reduced BMD at lumbar spine and circulating cytokines levels was carried out in acromegalic patients. In addition we evaluated the effect of acute octreotide administration on serum TNF-alpha and IL-I concentrations. Eleven patients with active acromegaly and eleven healthy age-, sex-, weight- and heightmatched subjects were enrolled in this study. BMD was significantly reduced at lumbar spine (0.80 +/- 0.29 g/cm2 vs 1.02 +/- 0.11 g/cm2; p < 0.01), but not at femoral neck level or at Ward's triangle level (0.92 + 0.15 g/cm2 vs 0.97 + 0.11 g/cm2, p = NS; and 0.74 +/- 0.16 g/cm2 vs 0.85 +/- 0.1 g/cm2, p = NS) when compared to controls. Baseline serum levels of TNF-alpha and IL-1 were in the normal range both in patients and controls. After acute octreotide administration, no differences in circulating TNF-alpha and IL-1 levels were found. In conclusion, acromegalic patients present a reduced BMD at lumbar spine but not at femoral neck level and Ward's triangle. Circulating cytokines such as TNF-alpha and IL-1 are in the normal range. These data suggest that cytokines are not involved in the pathogenesis of GH-excess induced osteoporosis. The possibility that the GH excess might affect bone turnover inducing an increase of cytokines acting by a paracrine/autocrine mechanism cannot be ruled out.     

Osteoporosis in rheumatoid arthritis

Patients with rheumatoid arthritis (RA) develop both periarticular and generalized osteoporosis. Periarticular osteopenia in appendicular bones occurs early in the course of RA and is one of the earliest radiological signs of RA. An uncoupled state in bone resorption-formation linkage, contributes to the development of periarticular osteopenia and it might be mediated through an increased productions of cytokines and prostaglandins by synovium and bone marrow. Accordingly, early suppression of rheumatoid synovitis is necessary for the prevention of periarticular osteopenia. Generalized osteoporosis is also common in RA and leads to increased risk of fractures. Generalized osteoporosis considered to be multifactorial and factors contributing to lumbar osteoporosis might be different from those to loss of appendicular bones, such as femur and radius. Corticosteroids and menopausal state are important risk factors for lumbar osteoporosis. Rheumatoid activity and reduced physical activity are also important determinants. According to the previous studies, however, the influence of functional impairment is more prominent in the femoral BMD compared to spinal BMD. In addition to control of RA and maintenance of physical activity, hormone replacement therapy (HRT) and bisphosphonate are possible agents for the treatment of osteoporosis in RA patients, especially postmenopausal women.     

Screening for osteopenia and osteoporosis: do the accepted normal ranges lead to overdiagnosis?

Osteoporosis is a common disease which causes significant morbidity and mortality and in many cases may be preventable. In the absence of fragility fractures the accepted method of identifying those at high risk is based upon bone mineral density (BMD) measurements with defined cut-off points. To correctly delineate normal from abnormal, reliable reference ranges appropriate to the observed population are required. We have studied the age-dependent changes in mean BMD and standard deviation at the lumbar spine and femoral neck in a normal population extracted from 4280 women screened for osteopenia and compared our findings with the manufacturer's normal range (MNR). The recent World Health Organization criteria for the diagnosis of osteopenia and osteoporosis using the 'manufacturer's young normal' (MYN) values and our 'study young normal' (SYN) values have been applied. The study normal population (SNP) included 2068 women (mixed social class; mean age 53 years, range 30-79 years). The distribution of mean lumbar spine BMD with age in SNP was generally similar to the MNR. In contrast mean femoral neck bone density from SNP was significantly different from the MNR, ranging from 3% to 12% lower in each 5-year group analysed (p < 0.05). Comparison of standard deviations in spine BMD in SNP against the fixed MNR standard deviation showed a statistically significant increase commencing at 45 years of age. The magnitude of this increase appeared to rise with age and remained significant in the 75- to 79-year age group (p < 0.05). In contrast, standard deviation in femoral neck BMD in SNP appeared relatively constant with age except in the group of women at and around the time of the menopause. The SYN value for mean lumbar spine BMD was 0.994 g/cm2 (cf. MYN value 1.047, p < 0.0001) with a standard deviation of 0.122 g/cm2 (cf. MYN 0.11, p = 0.0005). Similarly our SYN value for femoral neck BMD was 0.787 (cf. MYN value 0.895, p < 0.0001) with a standard deviation of 0.109 (cf. MYN value 0.10, p = 0.0027). Using SYN values 36% (748) for the spine and 33% (675) for the hip of our normal population are classified as osteopenic or osteoporotic. Using MYN values increases the proportion of women classified as osteopenic or osteoporotic to 52% (1078) for the spine and 68% (1409) for the femur. If both sites of measurement are considered simultaneously SYN classifies 46% (952) as either osteopenic or osteoporotic at one or other site, which is increased to 73% (1513) when the MYN values are used. We observe that manufacturer's reference ranges may not be appropriate for the local population and may lead to an erroneously high diagnosis of osteopenia and osteoporosis, which would lead to unnecessary patient anxiety and perhaps errors regarding treatment.     

Prediction of bone loss in patients with primary hyperparathyroidism using quantitative bone SPECT

Bone loss is a major complication of primary hyperparathyroidism (PHPT), and it has significant implications in the treatment of this disease. Bone turnover was measured in patients with PHPT, using quantitative bone SPECT (QBS), to determine if the rate of bone loss could be predicted before a significant decrease in bone mass occurs. METHODS: Forty-six patients were included in the study. QBS and bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) were done at baseline. The percent deviation of QBS in patients with PHPT from the values in normal matched controls was calculated. BMD was measured again after a mean of 17.5 mo in 38 patients, and in 29 patients a repeat BMD study was done after a mean of 41.4 mo. The change in BMD in patients with high and normal QBS values was compared using the nonparametric Mann-Whitney test. Regression analysis tested the correlation between baseline QBS values and BMD changes over time. RESULTS: For the FN, there was a statistically significant difference in the BMD change between patients with high and normal QBS values for short-term follow-up (-2.82%+/-4.80% versus 1.45%+/-4.67%, p < 0.05) and for long-term follow-up (-3.53%+/-5.34% versus 0.92%+/-2.40, p < 0.02). There was a negative correlation in the FN, r=-0.48 between QBS values and the percentage of change in BMD. There was no significant difference between the percentage of change in BMD in the LS in patients with high and normal QBS values for either short- or long-term follow-up. CONCLUSION: The results of this study show that QBS can predict bone loss in the FN in patients with PHPT. QBS can thus indicate the need for surgery at an early stage of the disease to prevent bone loss.     

Insulin-like growth factor-I in men with idiopathic osteoporosis

The etiology of osteoporosis in most men without a history of alcohol abuse, hypogonadism, or glucocorticoid excess is unknown. Several histomorphometric reports have demonstrated a reduction in indices of bone formation. We tested the hypothesis that the putative reduction in bone formation in men with idiopathic osteoporosis may be related to deficiencies in skeletal mechanisms that are mediated by insulin-like growth factor I (IGF-I). Twenty-four middle-aged men (50.5 +/- 1.9 yr) with severe idiopathic osteoporosis (mean lumbar spine T-score -3.5 +/- 0.16) were studied. The following biochemical indices were all normal: serum calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, testosterone, osteocalcin, carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, urinary calcium, and collagen crosslinks. Parathyroid hormone level was in the lower range of normal, 25 +/- 2 pg/mL (nl: 10-65). Mean serum IGF-I level was also in the lower range of normal, 157.9 +/- 7.6 ng/mL (normal age-matched range, 140-260 ng/mL). Eight men had IGF-I levels that were below 140 ng/mL. The mean IGF-IZ score was -0.75, significantly different from the expected mean of zero (P = 0.0002). IGF-I was correlated negatively with age (r = -0.49, P < 0.02). With age held constant, serum IGF-I accounted for 15% of the variance in lumbar bone mineral density (BMD; P < 0.001). The osteocalcin concentration correlated well with bone density at the distal 1/3 radius (r = +0.44; P < 0.002). Histomorphometric analysis of bone biopsy specimens showed significant reductions in cancellous bone volume (31%; P < 0.001), cortical width (28%; P < 0.05), osteoid surface (33%; P < 0.01), and bone formation rate (54%; P < 0.01) when results were compared with age-matched control subjects. Percent eroded surface was normal and was correlated inversely with serum IGF-I levels (r = -0.5; P < 0.04). These results suggest that serum IGF-I levels are reduced in men with idiopathic osteoporosis and that IGF-I correlates with and may contribute to the reduction in lumbar spine bone mass density (BMD). The low IGF-I levels may reflect the reduction in bone formation demonstrated by histomorphometry. Insights into the etiology of idiopathic osteoporosis in men may be revealed by further studies of the IGF-I axis.     

Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer: a double-blind, placebo-controlled study

PURPOSE: To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis. PATIENTS AND METHODS: Fifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment. RESULTS: Main outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group, there was an increase in BMD in the risedronate group. On treatment withdrawal, bone loss ensued, which suggests that treatment needs to be continuous to maintain a protective effect on bone mass. At 2 years, the mean difference (+/- SEM) between groups was 2.5% +/- 1.2%, (95% confidence interval [CI], 0.2 to 4.9) at the lumbar spine (P = .041) and 2.6% +/- 1.1%, (95% CI, 0.3 to 4.8) at the femoral neck (P = .029). Similar results were observed at the hip trochanter. Results by stratum indicate a beneficial, although partial, effect of tamoxifen in reducing bone loss. Risedronate was well tolerated and showed a good safety profile, with no evidence of laboratory abnormalities. CONCLUSION: Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer.     

Maintenance of bone mass in patients receiving dialytic therapy

To determine what factors contribute to and change bone mineral density (BMD) in dialysis patients, serial lumbar spine dual x-ray absorptiometry studies were analyzed by stepwise regression analysis in 67 black dialysis patients. The patients were 50.5 +/- 2.0 years of age (mean +/- SE) and 49% were men; the patients had received dialytic therapy for 3.7 +/- 0.5 years. The mean initial BMD z-score was 0.147 +/- 0.182. By cross-sectional analysis, the BMD increased in the male and premenopausal female patients but decreased in the postmenopausal female patients by 2.5% g/cm2/decade of life, less than that observed in black patients with normal renal function. Univariate analysis and stepwise regression analysis demonstrated radiographic evidence of osteopenia (beta-coefficient = -0.180 +/- 0.050; P = 0.001) and prior parathyroidectomy (beta-coefficient = 0.133 +/- 0.070; P = 0.054) as the only variables significantly correlated to the BMD. The effects of biochemical variables and different treatments on the delta BMD, calculated as the difference between each patient's first and second BMDs divided by the interval in years, were evaluated by stepwise regression analysis in 41 patients. The mean interval between the two BMDs was 18.4 +/- 1.02 months (range, 5 to 34 months) and the delta BMD was 0.025 +/- 0.018 g/cm2/yr, increasing in 65% of the patients. By univariate and stepwise regression analysis, the mean monthly serum total alkaline phosphatase concentration was the only variable that correlated with the delta BMD (beta-coefficient = 0.0001; P = 0.030).(ABSTRACT TRUNCATED AT 250 WORDS)     

Predicting clinical discordance of bone mineral density

OBJECTIVE: To identify clinical and lifestyle factors that may predict clinical discordance of bone mineral density (BMD) in otherwise healthy perimenopausal and postmenopausal women referred for bone densitometry. MATERIAL AND METHODS: Data from 304 white women referred for bone densitometry were retrospectively reviewed in order to determine predictors of BMD status at the lumbar spine, femoral neck, and distal radius. In addition, a cross-validation study in a further independent sample of 50 patients was undertaken. Dual-energy x-ray absorptiometry of all three sites was performed, and T-scores were determined with use of standard criteria established by the World Health Organization. Covariables including age, postmenopausal status, years since menopause, use of alcohol and cigarettes, family history of osteoporosis, exercise, height, weight, and body mass index were analyzed by canonical discriminant functions. RESULTS: Seventy-six patients (25%) had normal BMD at all three sites (group A); 55 patients (18%) had osteopenia or osteoporosis at all sites (group B); and 173 patients (57%) showed regional discordance of BMD (group C). Menopausal status, years since menopause, use of alcohol and cigarettes, exercise levels, and weight allowed distinct separation of these three groups by using the plot of one canonical discriminant function against the other. When tested, this method of assignment correctly predicted the regional BMD status in 38 of 50 women (76%) in the independent sample. CONCLUSION: Thus, the combination of certain clinical and lifestyle factors may be helpful in predicting variations in the clinical classification of BMD in an ambulatory healthy perimenopausal or postmenopausal woman.     

Association between insulin-like growth factor I and bone mineral density in older women and men: the Framingham Heart Study

Few studies of the GH axis and bone have focused specifically on elderly people. The objective of this study was to determine the association between insulin-like growth factor I (IGF-I) and bone mineral density (BMD) in 425 women and 257 men aged 72-94 who participated in the Framingham Osteoporosis Study component of the Framingham Heart Study in 1992-1993. Serum IGF-I level was determined by RIA. BMD at three femoral sites and the lumbar spine was determined by dual x-ray absorptiometry, and at the radius by single-photon absorptiometry. IGF-I level was positively associated with BMD at all five sites (Ward's area, femoral neck, trochanter, radius, and lumbar spine) in women after adjustment for weight loss and other factors (P < or = 0.01) and protein intake in a subset of participants (0.006 < P < 0.07). A threshold effect of higher BMD was evident at each of the 3 femoral sites and the spine (P < 0.03) but not at the radius for women in the highest quintile of IGF-I (> or = 179 g/liter) vs. those in the lowest four quintiles. IGF-I was not significantly associated with BMD in men. These results indicate that higher IGF-I levels are associated with greater BMD in very old women, and suggest that future clinical trials employing GH may have a role in the development of treatments for older women with osteoporosis.