High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women.

Animal studies demonstrated that phytoestrogen had a protective effect against bone loss after ovariectomy. However, data on dietary phytoestrogen intake as well as its relationship with bone mineral density (BMD) in human are not available. Six hundred fifty southern Chinese women, aged 19 to 86 yr, were recruited to determine their dietary phytoestrogen intake by a food frequency questionnaire. BMDs at the lumbar spine and hip region were measured using dual energy x-ray absorptiometry. The subjects were analyzed according to various tertiles of phytoestrogen intake. Among the postmenopausal women (n = 357), significant differences in the lumbar spine (L2-4) BMD (0.820 +/- 0.145 vs. 0.771 +/- 0.131 g/cm2, P < 0.05) and Ward's triangle BMD (0.450 +/- 0.151 vs. 0.415 +/- 0.142 g/cm2; P < 0.05) were found between the highest and lowest intake of isoflavone after adjusting for age, height, weight, years since menopause, smoking, alcohol consumption, HRT usage, and daily calcium intake. Women with the highest intake of isoflavone had significantly lower levels of serum PTH (19.38 +/- 14.61 vs. 26.56 +/- 11.19 pg/ml; P < 0.05), osteocalcin (4.95 +/- 3.61 vs. 6.69 +/- 5.05 mg/liter; P = 0.05), and urinary N-telopeptide (34.18 +/- 25.31 vs. 49.66 +/- 41.00 nmol bone collagen equivalents/mmol creatinine; P < 0.05) when compared with those with the lowest intake of isoflavone. No association between dietary phytoestrogen intake and BMDs was seen in the premenopausal women with high endogenous E (n = 293). In conclusion, postmenopausal women with habitually high intake of dietary isoflavone are associated with higher BMD values at both the spine and hip region. Customarily high isoflavone intake may help to reverse the state of secondary hyperparathyroidism associated with E withdrawal and hence lower the rate of bone turnover in postmenopausal women.     

Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2-year study

We investigated the effect of alendronate on calcium, PTH, and bone mineral density in 27 female and 5 male patients with primary hyperparathyroidism. The treatment group [n = 14; T score < or = -2.5 SD at the femoral neck (FN) or T < or = -1.0 SD plus previous nonvertebral fracture] was given alendronate 10 mg/d for 24 months. The second group (n = 18; T score > -2.5 SD at the FN) was untreated. Biochemistry was repeated at 1.5, 3, 6, 12, 18, and 24 months, and dual-energy x-ray absorptiometry at 12 and 24 months. There were no significant between-group baseline differences in calcium, creatinine, or PTH. Alendronate-treated patients gained bone at all sites [lumbar spine (LS), 1 yr gain, +7.3 +/- 1.7%; P < 0.001; 2 yr, +7.3 +/- 3.1%; P = 0.04). Untreated patients gained bone at the LS over 2 yr (+4.0 +/- 1.8%; P = 0.03) but lost bone elsewhere. Calcium fell nonsignificantly in the alendronate group between baseline (2.84 +/- 0.12 mmol/liter) and 6 wk (2.76 +/- 0.09 mmol/liter), with a nonsignificant rise in PTH (baseline, 103.5 +/- 14.6 ng/liter; 6 wk, 116.7 +/- 15.6 ng/liter). By 3 months, values had reverted to baseline. In primary hyperparathyroidism, alendronate is well tolerated and significantly improves bone mineral density at the LS (with lesser gains at FN and radius), especially within the first year of treatment. Short-term changes in calcium and PTH resolve by 3 months.     

Chylomicron remnant metabolism studied with a new breath test in postmenopausal women with and without type 2 diabetes mellitus

OBJECTIVES: The kinetic basis for the effect of type 2 diabetes mellitus (DM) on postprandial lipoproteins has not been fully established. We investigated chylomicron remnant metabolism using a stable isotope breath test and fasting measurements of plasma apolipoprotein (apo) B-48 and apoC-III concentrations in postmenopausal women with and without type 2 DM. PATIENTS: Twenty-four postmenopausal women without DM and 14 postmenopausal women with diet-controlled DM of similar age and body mass index (BMI) were studied in the postabsorptive state. METHODS: The fractional catabolic rate (FCR) of an intravenously injected chylomicron remnant-like emulsion was determined from the appearance of 13CO2 in the breath using isotope-ratio mass spectrometry and multicompartmental modelling. apoB-48, a marker of particle number of intestinal lipoproteins, was determined immunoelectrophoretically. apoC-III was measured by immunoturbidimetric assay. RESULTS: Compared with the nondiabetic women, the women with DM had significantly higher plasma apoB-48 concentration (16.40 +/- 1.18 mg/l vs. 13.0 +/- 0.9 mg/l; mean +/- standard error mean; P = 0.021), higher plasma apoC-III concentration (204.24 +/- 15.18 mg/l vs. 170.74 +/- 10.75 mg/l; P = 0.042) and lower FCR of the chylomicron remnant-like emulsion (0.06 +/- 0.05 pools/h vs. 0.12 +/- 0.02 pools/h; P < 0.001). In the diabetic patients, the FCR of the emulsion was correlated significantly with plasma apoB-48 levels (r = -0.641, P = 0.007) but not with apoC-III levels. CONCLUSIONS: In postmenopausal women, diabetes mellitus appears to decrease the catabolism of chylomicron remnants and result in an accumulation of these particles in plasma. This may chiefly be due to decreased clearance by hepatic receptors related to an effect of insulin resistance. Impairment in the catabolism of chylomicron remnants may contribute to increased risk of atherosclerosis in postmenopausal women with type 2 diabetes mellitus.     

Bone mineral density in acromegaly: the effect of gender,disease activity and gonadal status

OBJECTIVE: Data on bone mineral density (BMD) in acromegaly are conflicting as most previous studies collectively evaluated eugonadal and hypogonadal patients of both sexes, with or without active disease. We have evaluated BMD in 152 acromegalic patients of both sexes with varying disease activity and gonadal status. DESIGN: Cross-sectional, retrospective. PATIENTS: We studied 152 acromegalic patients (99 women aged 26-72 years, and 53 men aged 21-75 years), 107 with active and 45 with controlled disease. Eighty-five patients had normal gonadal status and 67 were hypogonadal. MEASUREMENTS: In all patients we measured serum GH levels by immunoenzimometric assay, and serum IGF-I levels by radioimmunoassay. BMD was assessed at spine L2-L4 (LS) and at femoral neck (FN) by dual energy X-ray absorptiometry; results are expressed as Z-values. RESULTS: We evaluated the effect of GH excess on bone at different sites in relation to gonadal status, disease activity and gender. At LS, in respect to the reference population, BMD (mean +/- SE) values were higher in eugonadal patients (active: 0.71 +/- 0.29, P < 0.02; controlled: 0.65 +/- 0.28, P < 0.05) and lower in hypogonadal ones (active: -0.64 +/- 0.35, 0.1 < P < 0.05; controlled: -1.05 +/- 0.36, P < 0.01), regardless of disease activity. On the contrary, at FN, BMD was higher than in the reference population, both in eugonadal (1.01 +/- 0.22, P < 0.001) and hypogonadal (0.63 +/- 0.17, P < 0.001) patients only in subjects with active disease, but not in those in which the disease was controlled (eugonadal: 0.31 +/- 0.23, P = ns; hypogonadal 0.04 +/- 0.28, P = ns). We did not observe any difference in BMD values according to gender both at LS (males vs. females -0.02 +/- 0.30 vs. 0.01 +/- 0.24, P = ns) or at FN (0.77 +/- 0.19 vs. 0.63 +/- 0.15, P = ns). CONCLUSIONS: The anabolic effect of GH excess on bone in acromegalic patients is: (i) gender-independent; (ii) evident at the spine only in eugonadal regardless of disease activity; (iii) evident at femoral neck only in the presence of active disease regardless of gonadal status.     

Metformin treatment is associated with an increase in bone mineral density in type 2 diabetes mellitus patients in China: A retrospective single center study

AimsTo investigate the association between metformin and bone mineral density (BMD) in a large cohort of Chinese patients with type 2 diabetes mellitus (T2DM).MethodsA total of 11,458 T2DM patients aged ≥40 years were included. Information on demographic, anthropometric and clinical characteristics was collected from medical records. BMD at lumbar spine (LS), femoral neck (FN), and total hip(TH) was assessed by dual-energy X-ray absorptiometry.ResultsOverall prevalence of osteopenia and osteoporosis was 37.4% and 10.3%, and was lower in patients on metformin (34.6% vs 38.3% and 7.1% vs 11.3%, both p < 0.001). Patients who had a lower BMI, older age, and lower estimated glomerular filtration rate (eGFR), had more osteoporosis, lower BMD (osteoporosis or osteopenia), and a lower T-score at LS, FN and TH. Metformin use and male sex was associated with a higher BMD. Metformin treatment was also independently associated with higher T-score at LS, FN and TH (β values of 0.120, 0.082 and 0.108; all p <0.001), and lower odds ratio of osteoporosis (OR = 0.779, 95%CI: 0.648–0.937, p = 0.008) or low BMD (OR = 0.834, 95%CI: 0.752 - 0.925, p = 0.001). However, when analyzed by sex, this association of a lower odds ratio for osteoporosis with metformin was only significant in women (OR= 0.775, 95% CI: 0.633–0.948; p = 0.013).ConclusionsMetformin treatment was associated with a higher T-score and a lower odds ratio of osteopenia and osteoporosis, especially in the female population, independent of age, BMI, and eGFR.     

Normal DXA bone mineral density but frail cortical bone in Turner's syndrome

CONTEXT: Patients with Turner's syndrome have normal bone mineral density by dual energy X-ray absorptiometry (DXA), but a predisposition for fractures. Quantitative ultrasonography (QUS) measures cortical bone strength. OBJECTIVE: To compare QUS with DXA in patients with Turner's syndrome. PATIENTS AND METHODS: Twenty-seven Turner's syndrome patients, aged 21.1 +/- 6.3 years (mean +/- SD), were evaluated by DXA, measuring two-dimensional bone mineral density (BMD), and QUS, measuring speed of sound (SOS) of the radius and tibia. The results were compared to sex- and age-matched (Ctr A, n = 53) and height-matched (Ctr B, n = 34) control groups. RESULTS: Fracture incidence per 1000 women years was 4.76 in Ctr A, 5 in Ctr B and 7.69 in Turner's patients. In Turner's syndrome patients, QUS results were significantly lower than in controls, whereas DXA Z-scores were not different from reference values. Correlation between tibia and radius SOS and height and age in controls (P < 0.0001) was not evident in Turner's syndrome. Oestrogen or growth hormone therapy had no effect on either QUS or DXA parameters. CONCLUSIONS: Bone fragility in Turner's syndrome is reflected by low SOS but not by DXA BMD. Low QUS, which assesses the cortical bone only, supports a defect in cortical bone in Turner's syndrome. Lack of SOS correlation with age, height and hormonal therapy in Turner's syndrome suggests a primary bone defect, rather than enhanced resorption of endocrine origin.     

High prevalence of early-onset osteopenia/osteoporosis after allogeneic stem cell transplantation and improvement after bisphosphonate therapy

Osteopenia/osteoporosis (O/O) has been associated with allogeneic stem cell transplantation (alloSCT). We retrospectively reviewed 102 patients undergoing a first alloSCT from 2000 to 2005 at our center to evaluate the prevalence of O/O < or =6 and >6 months post-alloSCT. Fifty-six patients did not have a dual energy X-ray absorptiometry (DXA) scan following alloSCT. Approximately half (n=13/27) of those with a first DXA scan < or =6 months post-alloSCT had O/O and a similar rate (n=9/19) was seen in those with a first DXA scan >6 months. There were no significant differences in patient characteristics between the normal and O/O groups. The dual femur (DF) appeared to be more vulnerable to alloSCT-induced bone mineral density (BMD) loss than the lumbar spine (LS), regardless of screening time. O/O patients were treated with bisphosphonates and 41% had a repeat DXA scan post-treatment. No patient developed jaw osteonecrosis and significant BMD improvement was seen at the LS (mean BMD, 1.03+/-0.13 vs 1.08+/-0.12, P=0.004) but not the DF (mean BMD, 0.84+/-0.06 vs 0.85+/-0.08, P=0.29), indicating BMD loss at the DF is more resistant than the LS to antiresorptive therapy. Our results demonstrate that O/O is an early and late complication post-alloSCT and bisphosphonate treatment reverses BMD loss at the LS.     

Factors influencing bone loss in rheumatoid arthritis: a longitudinal study

OBJECTIVES: To assess the occurrence of bone loss in rheumatoid arthritis (RA) and to determine the factors influencing bone loss (particularly the usefulness of bone turnover markers) over an 18-month period. METHODS: A total of 51 patients were studied, 6 men and 45 females (of whom 35 were menopausal). Their mean age was 56 +/- 10 years and the mean RA duration was 12 +/- 10 years. Twenty-eight (55%) were receiving corticosteroids (10 mg/day for a mean duration of 6 +/- 5 years). Several clinical and biological parameters reflecting disease activity or severity were recorded both at the 0 and 18-month investigations. Bone turnover was assessed at baseline by measuring the serum levels of 4 biological markers. Three of them reflected bone formation, i.e., procollagen type I C-terminal propepeptide (PICP), procollagen type I N-terminal propeptide (PINP) and osteocalcin (OC). The fourth, procollagen type I-C terminal telopeptide (ICTP), reflected bone resorption. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry both at the lumbar spine (LS) and femoral neck (FN) at baseline and 18 months later. RESULTS: Bone loss occurred both at the LS: 2.1%, [95% CI: 0.8%-3.4%, P < 0.005] and femoral neck: 3.1%, [95% CI: 1.1%-5.1%, P < 0.005]. Bone loss was markedly increased for postmenopausal women at the FN: 5.3% [95% CI: 2.9%-7.6%, P < 0.005]. Bone loss was not statistically significantly different between users and non-users of steroids. Bone loss at the LS was significantly correlated with both osteocalcin (r = 0.51, P < 0.01) and ICTP levels (r = 0.32, P < 0.05). FN bone loss was correlated with the osteocalcin level only (r = 0.34, P < 0.05). Fast losers (bone loss at the LS above the median) had higher OC (P < 0.01) and ESR (P < 0.05) levels at baseline as compared with slow losers (bone loss at the LS below the median). CONCLUSION: Bone loss occurs in RA particularly at the FN and seems to be influenced by increased bone turnover and high levels of inflammation.     

Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing's syndrome: a prospective, long-term study

OBJECTIVE: Endogenous Cushing's syndrome (CS) is associated with bone loss and an increased risk of fractures. However, the long-term outcome of treatment on bone health has not been adequately clarified. DESIGN: We followed 33 patients with active CS prospectively before and twice after treatment (mean follow-up 33 (n = 25) and 71 months (n = 18), respectively). The patients were compared to age-, sex- and body mass index (BMI)-matched controls, also followed longitudinally. METHODS: Bone mineral indices (bone mineral density (BMD), bone mineral content (BMC) and bone area) were evaluated in the lumbar spine (LS), femoral neck (FN), and total body (TB) by dual-energy X-ray absorptiometry (DXA). Biochemical markers of bone turnover were assessed by serum levels of osteocalcin and C-terminal telopeptides of Type-1 collagen (CTX-1). RESULTS: Mann-Whitney rank sum tests showed that BMD of the LS, FN and TB was reduced by 14.8% (P < 0.001), 15.7% (P < 0.001), and 9.2% (P < 0.001) in CS vs. controls at baseline, with markedly reduced serum osteocalcin (P = 0.014) and increased CTX-1 (P = 0.012) levels, but no correlation between markers. At first follow-up, BMD was increased in LS (7.9%, P < 0.001) and FN (3.5%, P = 0.003) compared to baseline. The time-dependent rise in BMD (LS (r = 0.59; P = 0.002) and FN (r = 0.52; P = 0.007); Spearman's rank correlation), in CS was paralleled by increased osteocalcin (275%, P < 0.001) and correlation between biochemical markers (r = 0.92, P < 0.001; Pearson's correlation). TB BMD did not increase significantly before the second follow-up, when BMD Z-scores were normalized in all three compartments. CONCLUSION: Our observations demonstrate restoration of coupled bone remodeling and normalization of bone mineral density in all measured skeletal compartments of treated CS patients after prolonged recovery, first significant in predominantly trabecular bone (i.e. lumbar spine).     

Osteoporosis and lung transplantation: a prospective study

STUDY OBJECTIVE: Osteoporosis is a well-recognized complication of lung transplantation that may significantly impair the quality of life of transplant recipients. We performed a prospective study of bone mineral density (BMD) before and after transplantation to determine the degree of bone mass loss associated with lung transplantation Patients and design: We conducted a prospective study of BMD in 28 patients with various end-stage respiratory diseases pretransplantation and 6 to 12 months posttransplantation. The BMD of the lumbar spine (LS) and femoral neck (FN) were measured. All 28 patients were treated only with vitamin D and calcium supplementation posttransplant. The primary endpoint was the percentage change in BMD. The secondary endpoint was the incidence of fractures posttransplant. A univariate analysis was conducted to determine the various risk factors associated with bone mass loss pretransplant and posttransplant. RESULTS: Prior to transplantation, moderate to severe bone disease was evident. The mean (+/- SD) pretransplant T score (the number of SDs from the peak bone mass) and Z score (the number of SDs from the age-matched mean) for the LS were -1.72 +/- 1.37 and -1.44 +/- 1.31, respectively. The mean pretransplant T score and Z score for the FN were -2.65 +/- 1.01 and -1.5 +/- 1.43, respectively. Within 6 to 12 months posttransplant, the mean BMD for the LS decreased by 4.76% (p < 0.001), while the mean BMD for the FN decreased by 5.3% (p < 0.001). Five of the 28 patients (18%) suffered osteoporotic fractures posttransplant, while no fractures were documented pretransplant. The cumulative steroid dose posttransplant was associated with a drop in BMD for the LS and FN (r = 0.39, p = 0.039 and r = 0.63, p < 0.001, respectively), while a negative association was found between cumulative steroid use pretransplant and baseline LS and FN T scores (r = -0.4, p = 0. 02 and r = -0.43, p = 0.023, respectively). CONCLUSION: Within 6 to 12 months after lung transplantation, there is a significant decrease in BMD at both the LS and FN levels (approximately 5%) despite vitamin D and calcium supplementation. This drop in BMD is associated with a relatively high incidence of osteoporotic fractures posttransplant.     

Comparison of quantitative ultrasound parameters with dual energy X-ray absorptiometry in pre- and postmenopausal women

BACKGROUND: Quantitative ultrasound (QUS) has been claimed as an alternative technique for risk assessment of hip fractures associated with osteoporosis. However, reports concerning modest correlations between QUS parameters and dual energy X-ray absorptiometry (DXA) in women raise questions about the reliability of QUS technology to predict bone mineral density (BMD). Partially, the lack of stronger correlations may be due to heterogeneity in bone architecture deterioration which may be more pronounced in older than in younger women. Therefore, it was thought important to study QUS/DXA interrelationships in subgroups of pre- and postmenopausal women. METHODS: We studied 217 pre- and postmenopausal women between the ages of 25 and 75 years, who were referred for a BMD measurement because of osteoporosis in at least one family member either in the first or in the second degree. All women had a calcaneal QUS and a DXA measurement at the lumbar spine, total hip and femoral neck. RESULTS: The linear regression coefficients between the QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) and DXA at the various sites in the group as a whole were 0.53 to 0.54 (P<0.0001). Significantly lower regression coefficients between BUA and DXA at the total hip and the femoral neck were found in premenopausal women (r=0.31 and 0.38, P<0.0001) compared to postmenopausal women (r=0.56 and 0.53, P<0.0001). For SOS there was no significant difference between the regression coefficients in the pre- and postmenopausal group. The overall prevalence of osteoporosis as assessed by DXA in the total group was 25% (6% in the pre- and 36% in the postmenopausal group). BUA failed to detect osteoporosis in all five premenopausal women but also in 20 out of 50 postmenopausal women with osteoporosis according to DXA measurements. SOS measurements were even worse in this respect. CONCLUSIONS: Linear regression coefficients between calcaneal QUS parameters and DXA are only modest considering a group of 25--75-year-old Dutch women. In the subgroup of premenopausal women correlations between BUA and BMD at the hip and femoral neck are worse compared to those in postmenopausal women. The predictive value of QUS parameters for BMD is limited, therefore it is not appropriate to use QUS as a surrogate for DXA.     

Hypothalamic-pituitary-adrenal activity in type 2 diabetes mellitus: role of autonomic imbalance

Symptomatic diabetic neuropathy has been found to be associated with hypothalamus-pituitary-adrenal (HPA) axis hyperfunction, but no data are available about HPA activity in diabetic patients with asymptomatic autonomic imbalance. To evaluate HPA axis activity in patients with type 2 diabetes mellitus (T2DM) in relation to the presence or the absence of subclinical parasympathetic or sympathetic neuronal dysfunction, we performed an observational study on 59 consecutive type 2 diabetic patients without chronic complications and/or symptoms of neuropathy or hypercortisolism. The following were measured: serum cortisol at 08:00 am and at midnight (F8 and F24, respectively), post-dexamethasone suppression cortisol, 24-hour urinary free cortisol (UFC), and morning corticotropin (ACTH). Deep-breathing (DB) and LS (LS) autonomic tests were performed to assess the parasympathetic function; postural hypotension test was performed to evaluate sympathetic activity. Patients were subdivided into 4 groups: subjects with parasympathetic failure (group A), sympathetic failure (group B), both para- and sympathetic failure (group C), and without autonomic failure (group D). Hypothalamus-pituitary-adrenal activity was increased in group A compared with group D (UFC, 48.6 +/- 21.4 vs 21.6 +/- 9.8 microg/24 h, P < .0001; ACTH, 27.0 +/- 8.6 vs 15.7 +/- 5.7 pg/dL, P < .01; F8, 20.4 +/- 4.5 vs 13.6 +/- 3.8 microg/dL, P < .05; post-dexamethasone suppression cortisol, 1.2 +/- 0.4 vs 0.8 +/- 0.6 microg/dL, P < .05, respectively) and group B (UFC, 26.3 +/- 11.0 microg/24 h, P < .0001; ACTH, 19.9 +/- 8.0 pg/dL, P < .05). Regression analysis showed that UFC levels were significantly associated with the deep-breathing test (beta = -0.40, P = .004) and tended to be associated with the lying-to-standing test (beta = -0.26, P = .065), whereas body mass index, glycated hemoglobin, and duration of disease were not. Type 2 diabetic patients with asymptomatic parasympathetic derangement have increased activity of HPA axis, related to the degree of the neuronal dysfunction.     

Bone turnover markers predict changes in bone mineral density after parathyroidectomy in patients with renal hyperparathyroidism

Objective Patients on long‐term dialysis may develop secondary hyperparathyroidism (SHPT), which causes varying degrees of bone mass loss. This condition is treated with parathyroidectomy (PTX). We investigated whether serial serum bone turnover markers could predict changes in bone mineral density (BMD) after PTX. Design and patients Renal patients on maintenance haemodialysis who received PTX for refractory SHPT (n = 26, male/female: 13/13; mean age: 48·6 ± 10·7 year) and control subjects without SHPT (n = 25) were prospectively followed for 1 year at two tertiary hospitals in Taiwan. Measurements Serum intact parathyroid hormone (iPTH), bone‐specific alkaline phosphatase (BAP) and type 5b tartrate‐resistant acid phosphatase (TRAP) were measured serially. Additionally, femoral neck (FN) and lumbar spine (LS) BMD were measured before and 1 year after PTX. Results After PTX, iPTH levels decreased markedly and persistently. BMDs increased in both the FN and LS, but particularly in the LS. Serum BAP progressively increased to a peak at 2 weeks after PTX. Serum TRAP levels progressively decreased over 6 months after PTX. In univariate correlation analyses, baseline iPTH correlated positively with T‐score changes in FN (r = 0·45, P = 0·021) and LS (r = 0·48, P = 0·013). In multivariate regression models, changes in FN T‐scores were negatively predicted by baseline BAP levels (r = ?0·615, P = 0·005) and baseline FN T‐scores (r = ?0·563, P = 0·012), and they were positively predicted by baseline TRAP(r = 0·6, P = 0·007). Changes in LS T‐scores were positively predicted by baseline TRAP values (r = 0·528, P = 0·01) and negatively predicted by the percentage change in BAP after 2 weeks (r = ?0·501, P = 0·015). Conclusions Parathyroidectomy provided marked, sustained improvements in BMD for up to 1 year. Furthermore, markers of bone turnover predicted 1‐year changes in FN and LS BMDs after PTX.     

骨定量超声测量及OSTA指数与绝经后妇女非椎骨骨折的关系

目的横断面社区研究分析绝经后妇女OSTA指数及多部位定量骨超声（quantitative ultasound,QUS）[超声速率（speed of sound,SOS）],探讨该两个指标预测非椎骨骨折的价值。方法采用以色列Sunlisht Omnisense7000P型QUS仪测量513例女性受试者非优势侧桡骨远端1／3、中指近节指骨及胫骨中段SOS。测量受检者身高、体重,计算OSTA指数,上门问卷形式询问骨折史。结果（1）271例绝经后妇女桡骨、指骨、胫骨SOS显著低于242例绝经前妇女,P〈0．001。（2）绝经后妇女非椎骨骨折组桡骨SOS低于无骨折组（P=0．044）,发生于绝经后的非椎骨骨折妇女,指骨SOS低于无骨折组（P=0．003）。（3）以OSTA〈-4、-4- -1、〉-1将绝经后妇女分为骨质疏松高、中、低风险3组。随骨质疏松风险增加,发生于绝经后的非椎骨骨折率明显升高（χ^2=6．370,P=0．041）,且桡骨、指骨、胫骨SOS显著下降。（4）OSTA取-1及指骨SOSt值取-1．95反映绝经后非椎骨骨折的敏感性分别为75％和81％,特异性分别为48％和40％,受试者工作特征曲线下面积（AUC）分别为0．64和0．66。两者结合敏感性为83％,特异性提高至84％,AUC为0．64。结论OSTA和QUS尤其是指骨SOS具有反映绝经后妇女非椎骨骨折的能力。这两种非常简单、廉价、无创伤性的检查方法有助于筛查高危骨折风险的绝经后妇女。     

Osteoporosis, mineral metabolism, and serum soluble tumor necrosis factor receptor p55 in viral cirrhosis

Liver cirrhosis is a risk factor for osteoporosis. Nevertheless, little is known about the mechanisms of bone mass loss in patients with viral cirrhosis. TNFalpha is a potent bone-resorbing agent. Serum concentrations of soluble TNF receptor p55 (sTNFR-55) correlate with clinical activity in liver cirrhosis. Our aim was to evaluate the possible role of sTNFR-55 in the pathogenesis of osteoporosis in patients with viral cirrhosis and its relationship with bone turnover markers. We studied 40 consecutive patients with viral cirrhosis and no history of alcohol intake and 26 healthy volunteers. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in the lumbar spine (LS) and femoral neck (FN). Patients with viral cirrhosis had reduced BMD (expressed as the z-score) in all sites [LS, -1.5 +/- 0.22 (P < 0.001); FN, -0.37 +/- 0.15 (P < 0.01)]. Serum concentrations of sTNFR-55 and urinary deoxypyridinoline, a biochemical marker of bone resorption, were significantly higher in patients with osteoporosis than in patients without osteoporosis (P < 0.001 and P < 0.05, respectively). Serum levels of sTNFR-55 correlated inversely with BMD in LS (r = -0.62; P < 0.005) and FN (r = -0.47; P < 0.05) and positively with urinary deoxypyridinoline (r = 0.72, P < 0.001). Our findings show that high serum concentrations of sTNFR-55 play a role in the pathogenesis of viral cirrhosis-associated bone mass loss and provide evidence of increased bone resorption related to the high serum sTNFR-55 levels.     

Low normal TSH levels are associated with low bone mineral density in healthy postmenopausal women

OBJECTIVE: Hyperthyroidism is accompanied by low bone mass. Because the reference range of TSH levels is defined statistically, some individuals with low normal TSH levels may have mild hyperthyroidism and reduced bone mass. We therefore determined whether serum TSH levels correlate with bone mineral density (BMD). DESIGN: A cross-sectional hospital-based survey. Participants Nine hundred and fifty-nine healthy postmenopausal women. MEASUREMENTS: We measured BMD at the lumbar spine and femoral neck using dual energy X-ray absorptiometry, and serum TSH concentrations using immunoluminometry. RESULTS: BMD at the lumbar spine and femoral neck increased with TSH level (P for trend < 0.001 at both sites). Even after adjustment for age, years since menopause and body mass index, subjects with low normal TSH levels (0.5-1.1 mU/l) had significantly lower BMDs at the lumbar spine (0.863 +/- 0.009 g/cm2 vs 0.900 +/- 0.009 g/cm2, P = 0.004) and femoral neck (0.660 +/- 0.006 g/cm2 vs 0.683 +/- 0.006 g/cm2, P = 0.006) than those with high normal TSH levels (2.8-5.0 mU/l), as well as a 2.2-fold increased risk of osteoporosis (95% confidence interval: 1.2-4.0). CONCLUSION: These results suggest that low normal TSH levels may not be physiological for postmenopausal women and, during treatment of hypothyroidism, may not be adequate for avoiding osteoporosis.     

Bone metabolism and the 10-year probability of hip fracture and a major osteoporotic fracture using the country-specific FRAX algorithm in men over 50 years of age with type 2 diabetes mellitus: a case–control study

The aim of the study was to evaluate the 10-year probability of hip fracture and a major osteoporotic fracture using the FRAX algorithm, vitamin D status, bone mineral density (BMD), and biochemical markers of bone turnover in men over 50 years of age with type 2 diabetes mellitus (T2DM). We estimated FRAX-predicted 10-year fracture probability, levels of 25-hydroxyvitamin D (25-OH-D), markers of bone turnover, and bone mineral density at the L1–L4 (lumbar spine (LS)) and femur neck (FN) in 68 men with T2DM and compared these with an age-matched group (n?=?68). The mean (range) age of the T2DM group was 61.4 (51–78)?years. The prevalence of hypovitaminosis D (25-OH-D <75 nmol/L) was 59 %. The mean (range) FRAX hip fracture and FRAX major osteoporotic fracture was 0.7 (0–2.8) and 3.2 (0–8.5)?%, respectively. BMD at the FN (0.974 vs. 0.915 g/cm², p?=?0.008) and LS (1.221 vs. 1.068 g/cm², p?<?0.001) was significantly higher in the T2DM cohort as compared to the healthy age-matched males. 25-OH-vitamin D (67.7 vs.79.8 nmol/L, p?<?0.001), crosslaps (0.19 vs. 0.24 μg/L, p?=?0.004), and osteocalcin (13.3 vs. 15.7 μg/L, p?=?0.004) were significantly lower in the T2DM group. There was no difference in FRAX-related fracture probability between the two groups. Acknowledging the limitations of our study size, we suggest that the increased BMD in T2DM and the noninclusion of T2DM as a secondary risk factor in the FRAX algorithm may be probable explanations for the discordance between literature-observed and FRAX-related fracture probabilities.     

Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus

CONTEXT: Visfatin (also known as pre-B cell colony-enhancing factor or PBEF) is a cytokine that is highly expressed in visceral fat and whose blood levels correlate with obesity. Originally isolated as a secreted factor that promotes the growth of B cell precursors and recently found to act as an insulin analog on the insulin receptor, its pathophysiological role in humans remains largely unknown. OBJECTIVES: In this study we investigated whether plasma visfatin level is altered in patients with type 2 diabetes mellitus (T2DM). DESIGN AND PATIENTS: Plasma visfatin as well as adiponectin and resistin concentrations were measured through ELISA in type 2 diabetic and nondiabetic subjects. RESULTS: A total of 61 patients with T2DM and 59 sex- and age-matched nondiabetic subjects were studied. Plasma visfatin was found to be elevated in patients with T2DM (31.9 +/- 31.7 vs. 15.8 +/- 16.7 ng/ml, P = 0.002). In contrast, adiponectin was decreased (4.3 +/- 2.5 vs. 30.8 +/- 10.3 microg/ml, P < 0.001), whereas plasma resistin level did not differ between the groups. Increasing concentrations of visfatin were independently and significantly associated with T2DM. Multiple logistic regression analysis revealed visfatin as an independent association factor for T2DM, even after full adjustment of known biomarkers. The association between adiponectin and T2DM was no longer significant after adjustments for body mass index or waist to hip ratio. In a multiple linear regression analysis, only waist to hip ratio was independently associated with plasma visfatin level. CONCLUSION: Our results indicate that visfatin may play a role in the pathogenesis of T2DM.     

Bone mineral density in patients with longstanding type 1 diabetes: Results from the Canadian Study of Longevity in Type 1 Diabetes

AimIt is currently unclear if longstanding type 1 diabetes (T1D) affects bone mineral density (BMD).MethodsBMD measured by dual-energy X-ray absorptiometry and history of fragility fracture was determined in 75 T1D participants with ≥50 years of diabetes duration and 75 age- and sex-matched non-diabetic controls. BMD T-scores were determined for the lumbar spine (LS), total hip (TH) and femoral neck (FN).ResultsT1D participants had median diabetes duration of 54 [52, 58] years, 41 (55%) were females, and mean A_1c was 7.3 ± 0.8%. T1D females had higher LS T-scores compared to female controls (?0.3 ± 1.2 vs. ?1.1 ± 1.4, p = 0.014), lower FN T-scores (?1.5 ± 1.0 vs. ?1.2 ± 0.9, p = 0.042) and more fragility fractures (7 (17%) vs. 1 (2%), p = 0.021). In T1D, higher A1c was associated with higher adjusted odds of fragility fracture (p = 0.006). T1D males and controls showed no difference in BMD or fractures.ConclusionsThere were no substantial differences in T-score between T1D and matched controls; however, T1D females showed higher BMD at the LS and possibly paradoxically higher fragility fractures compared to matched controls. These findings suggest that lower T-scores may not be associated with a history of fragility fracture in females with longstanding T1D and that other factors should be investigated.     

Diabetes and premature menopause: is their co-existence detrimental to the skeleton?

OBJECTIVE: Premature menopause is a known risk factor for osteoporosis, whilst the influence of type 2 diabetes on bone mineral density (BMD) is still controversial. DESIGN AND METHODS: BMD values assessed by dual-energy X-ray absorptiometry (DXA) in L2-L4 vertebrae and the femoral neck (FN) of 40 diabetic women with premature menopause (D-EMP) were compared with those of 60 non-diabetic, prematurely menopausal women (EMP) and 60 diabetic women with normal menopause (D-NMP) who had been matched by age and body mass index (BMI). In all women, the time elapsed since menopause ranged between 10 and 25 years and the duration of diabetes exceeded 75% of the postmenopausal time period. The age of D-EMP women was 58.7+/-5 years (mean+/-1 s.d.), age at menopause 39.5+/-2.7, years since menopause 18.6+/-4.9, BMI 27.8+/-4.3 kg/m(2) and duration of diabetes 13.9+/-3.9 years. RESULTS: Vertebral BMD values of D-EMP women were significantly higher than those of EMP women (0.908+/-0.135 vs. 0.817+/-0.14 g/cm(2), P = 0.002), although there was no significant difference between D-EMP and D-NMP women (0.886+/-0.15 g/cm(2)). No significant differences were observed in FN BMD values between all groups. Age-adjusted BMD values (Z scores) of D-EMP women were higher than EMP women in both anatomic sites (P < 0.01), but did not differ from D-NMP women. In contrast to the other two groups, no statistically significant correlation was observed in D-EMP women between the BMD values of either anatomic area and the time elapsed since menopause. HbA(1c) values were positively correlated only to vertebral BMD values of the D-EMP group (P < 0.05). No correlation was observed between the BMD values and the duration of diabetes either in D-EMP or in D-NMP women. CONCLUSIONS: Type 2 diabetes seems to positively affect the mineral density of the trabecular bone in women with premature menopause. The duration of diabetes does not appear to influence bone mass.