Biochemical Parameters Of Bone Turnover Research Articles

Evaluation of Bone Mineral Density in Prepubertal Children with Familial Mediterranean Fever

Objective: Familial Mediterranean Fever (FMF) is a hereditary autosomal recessive chronic periodic inflammatory disease, characterized by recurrent fever polyserositis and skin manifestations. The aim of this study was to investigate the bone mineral density (BMD) in prepubertal children with FMF and to determine the relationship between bone density and demographic, laboratory characteristics of the disease. Material and Method: Thirty two previously diagnosed, attack-free, prepubertal FMF patients who were receiving regular colchicine treatment were included in the study. Demographic and clinical data of patients, acute phase reactants, biochemical parameters of bone turnover, bone age, and L1-L4 vertebral mineral density were evaluated. The results of the patients were compared with values determined for healthy Turkish children. Results: All of the patients had z-scores which were greater than -2. Acute phase values and bone metabolism markers were within normal limits. No correlation was found between the aBMD Z-score and demographic data, acute phase reactants and bone metabolism markers. There was a negative correlation between delay in diagnosis and aBMD Z- score. Conclusion: Although aBMD Z-scores were normal in children with FMF the aBMD Z score was found to be lower in children who had had a delay in treatment. Early initiated colchicine therapy is important for optimal bone health in these patients.

Primary Aldosteronism and Bone Metabolism: A Systematic Review and Meta-Analysis.

BackgroundCurrently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis. This problem is worthy of attention because secondary osteoporosis is always potentially reversible, which affects the selection of treatment for PA to some extent. The present systematic review will assess and summarize the available data regarding the relationship between PA and osteoporosis.MethodsPubmed and Embase were searched for clinical trials related to the association between PA and bone metabolism. The results were limited to full-text articles published in English, without restrictions for the publication time. The quality of clinical trials was appraised, and the data were extracted. Biochemical parameters of bone turnover in PA patients were assessed using random-effect meta-analysis. Descriptive analysis was performed for other parameters, for data is insufficient.ResultsA final total of 15 articles were included in this review. The meta-analysis of six studies showed that subjects with PA had higher serum PTH levels (MD=21.50 pg/ml, 95% CI (15.63, 27.37), P<0.00001) and slightly increased urinary calcium levels (MD = 1.65 mmol/24 h, 95% CI (1.24, 2.06), P < 0.00001) than the EH controls. PA is associated with an increased risk of bone fracture. Bone loss in patients with PA may be reversed by MR antagonists or adrenal surgery.ConclusionsPA may be a secondary cause of osteoporosis and is associated with an increased risk of bone fracture. The clarification of the relationships between PA and bone metabolism requires additional prospective randomized controlled studies in a large sample.

Eighteen-Year Effect of Androgen Therapy on Bone Mineral Density in Trans(gender) Men.

The study explores the influence of long-term androgen supplementation (18 years) on bone metabolism in trans(gender) men. Thirty five trans(gender) men aged (47±4) were treated with adequate dose of testosterone. BMD was measured by DEXA at lumbar spine and neck and T score was determined. Biochemical parameters of bone turnover were measured in all patients. As compared with female and male age matched controls they showed a not significantly different T-score at spine [1.213±0.15 in trans(gender) men vs. 1.192±0.19 in females and 1.203±0.06 g/cm2 in males (p<0.01)]. BMD in the hip skeleton in trans(gender) men (0.950±g/cm2) was statistically higher than females (0.822±0.09) but not statistically different from normal males 0.988±0.06). Circulating biochemical markers of bone formation, and resorption were not different between the trans(gender) men, and matched controls. We conclude that BMD at the hip (site rich in cortical bone) after adequate dose of testosterone therapy is higher while it is not different at the spine (trabecular bone) in trans(gender) men even after 18 years of testosterone administration.

A lower proportion of circulating active parathyroid hormone in peritoneal dialysis does not allow the pth inter-method adjustment proposed for haemodialysis.

Parathyroid hormone (PTH) shows a strong correlation with histomorphometric and biochemical parameters of bone turnover, however its measurement presents limitations due to inter-method variability. Circulating PTH is a mixture of peptides, but only on its whole form (1-84 PTH) is responsible of PTH biological activity. Carboxyl-terminal fragments exhibit antagonist actions and their proportion differs at each stage of chronic kidney disease, as consequence of differences on their renal clearance. The aim of this study is to evaluate possible differences in the proportion of these fragments according to dialysis type: haemodialysis (HD) or peritoneal dialysis (PD). Serum total (Ca) and ionized calcium (iCa), phosphate (P), carboxyl-terminal telopeptides of collagen type I (BCTx) were measured in 73 patients on PD (46 men and 27 women with an age between 22 and 82 years). PTH was quantified by six second generation assays (one isotopic and five chemiluminescence assays) and by one third generation PTH method. Mean serum levels of Ca, iCa, P and BCTx were 9.03, 4.76, 4.73 mg/dl and 1181 pmol/l, respectively. Significant differences were observed in PTH values according to the method used. Adjustment of PTH results to PTH Allegro (Nichols) range of 150-300 nmol/l in PD patients showed higher values than those assessed previously for HD population. The percentage of biologically active 1-84 PTH as the 1-84 PTH/ 7-84 PTH ratio in PD were significantly lower than in HD patients, reflecting the higher proportion of 7-84 PTH circulating fragments for a given intact PTH result in PD. PD patients have a higher proportion of 7-84 PTH circulating fragments. Consequently, the inter-method adjustment algorithms proposed for HD patients are not useful for PD patients. This study proposes alternative algorithms for PTH inter-method adjustment to be applied in PD.

Effects of carbamazepine on serum parathormone, 25- hydroxyvitamin D, bone specific alkaline phosphatase, C-telopeptide, and osteocalcin levels in healthy rats

It is still not completely clear whether carbamazepine causes alterations in vitamin D status and in bone metabolism. The objective of this study was to investigate the effects of carbamazepine on serum levels of 25-hydroxyvitamin D and on biomarkers of bone formation and resorption in healthy rats. Levels of calcium, 25- hydroxyvitamin D, parathormone, C-telopeptide, bone specific alkaline phosphatase and osteocalcin were measured in 3 groups of rats consisting of controls (n=10), isotonic saline solution group (n=10) and carbamazepine group (n=10). Mean calcium levels were found to be significantly lower in healthy controls in comparison to isotonic saline solution and carbamazepine groups (10.0±0.24, 10.81±0.16, 10.93±0.22 mg/dL, respectively, p<0.05). Mean levels of 25- hydroxyvitamin D, were found to be significantly higher in control group compared to isotonic saline solution group (25- hydroxyvitamin D; 25.91±1.12, 19.99±0.99 ng/mL, respectively, p<0.01). Mean levels of parathormone and osteocalcin were found to be significantly higher in control group compared to isotonic saline solution group and carbamazepine group. Parathormone levels were measured as 3.46±0.83, 1.08±0.08, 0.94±0.02 pg/mL, respectively (p<0.01). Osteocalcine levels were measured as 1.66±0.001, 1.32±0.002, 1.32±0.001 ng/mL, respectively (p<0.001). A significant difference in terms of mean serum bone specific alkaline phosphatase and C-telopeptide levels among groups was not observed. The main outcome of this prospective study in healthy rats showed no change in biochemical parameters of bone turnover during treatment with carbamazepine.

Osteocalcin and selected biochemical parameters of bone turnover in healthy subjects

Osteocalcin (OC) is non-collagenous bone matrix protein produced by osteoblasts. OC binds to hydroxyapatite and is deposited in the bone matrix. Concentration of OC in the blood seems to reflect both osteogenesis and increased bone metabolism and depends on age, sex, menopausal status. The aim of our study was to evaluate changes in the concentration of osteocalcin and selected biochemical parameters of bone turnover in different stages of life in healthy people. We found that the mean serum levels of OC were significantly greater in women than in men. The highest OC levels were found in men under the age of 30 with a decrease in the fourth decade of life. In the group of women of up to 40 years of age, OC concentrations were comparable with the equivalent group of men. The lowest concentration of OC was found in the age group 40-49, with the significant increase in the subsequent decades of life. In both men and women, we found a significant correlation of OC with the calcium concentrations and alkaline phosphatase activity. Osteocalcin determinationa, particulary in women, may be useful laboratory parameters of osteoporosis process.

175. Sleep and cytokines in early gestation: Possible mechanisms for adverse pregnancy outcomes

Systemic infection and inflammation in men are associated with bone loss. Rodent studies have elucidated the pathways mediating the effects of bacterial lipopolysaccharide (LPS), activated immune cells and hormones on bone. Here we investigate the changes in biochemical parameters of bone turnover following human endotoxemia, an experimental model of self-limiting systemic infection and inflammation.Ten healthy men received in a randomised, placebo-controlled, cross-over trial once placebo and once 2 ng/kg Escherichia coli endotoxin (LPS). During the following 6 h we monitored parathyoid hormone (PTH) and osteopontin (OPN), a multifunctional protein related to bone pathophysiology, as well as biochemical markers of bone turnover: C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). In LPS sessions there was a transient fall in PTH at 3 h (p = 0.009) and a nearly two-fold increase in OPN levels after 6 h (LPS: 155 ± 19 pg/ml; placebo: 85 ± 13 pg/ml, p < 0.001). LPS gradually reduced CTX levels (LPS: 0.44 ± 0.4 pg/ml; placebo: 0.59 ± 0.06 pg/ml, p = 0.003), P1NP showed a peak at 4 h (LPS: 89.9 ± 14.7 pg/ml; placebo: 75 ± 9.7 pg/ml, p = 0.028) and circulating OC did not change.The early human response to systemic endotoxemia boosts osteopontin levels and modifies bone biomarkers, indicating a decrease in the lytic activity of osteoclasts, accompanied by an increase in the activity of immature osteoblasts. These changes might present the acute phase response of immune and bone cells to bacterial stimuli in men.

Serum resistin in older patients with hip fracture: Relationship with comorbidity and biochemical determinants of bone metabolism

ObjectivesTo determine the relationship of serum resistin concentrations to biochemical determinants of bone metabolism, comorbidity and outcomes in patients with hip fracture (HF). MethodsIn 256 consecutive patients (mean age 81.9±7.8years; 71.1% women) serum levels of resistin (determined by ELISA), biochemical parameters of bone turnover and mineral metabolism as well as routine haematological and biochemical parameters were measured. Clinical data were recorded prospectively. ResultsIn multivariate analysis cervical HF (OR=1.81; 95% CI 1.05–3.11), diabetes (OR=2.60; 95% CI 1.23–5.51) and history of stroke (OR=2.67; 95% CI 1.17–6.13) were significant independent predictors of higher resistin levels (⩾16.26ng/ml, median value). The independent correlates of serum resistin levels in patients with cervical HF were serum osteocalcin and magnesium (both negatively associated) and in patients with trochanteric HF, serum PTH, calcium and age (all positively associated). Resistin and glomerular filtration rate were the only independent (inverse) predictors of serum osteocalcin. Resistin levels on admission did not predict short-term outcomes. ConclusionsIn older patients with HF there is a significant association of higher resistin levels with cervical fracture, type 2 diabetes and history of stroke, which is partly influenced by the reciprocal interaction between resistin and osteocalcin. However, the design of the study does not prove causality and further prospective studies are needed to clarify these relationships.

Changes in osteopontin and in biomarkers of bone turnover during human endotoxemia

Systemic infection and inflammation in men are associated with bone loss. Rodent studies have elucidated the pathways mediating the effects of bacterial lipopolysaccharide (LPS), activated immune cells and hormones on bone. Here we investigate the changes in biochemical parameters of bone turnover following human endotoxemia, an experimental model of self-limiting systemic infection and inflammation. Ten healthy men received in a randomised, placebo-controlled, cross-over trial once placebo and once 2 ng/kg Escherichia coli endotoxin (LPS). During the following 6 h we monitored parathyoid hormone (PTH) and osteopontin (OPN), a multifunctional protein related to bone pathophysiology, as well as biochemical markers of bone turnover: C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). In LPS sessions there was a transient fall in PTH at 3 h ( p = 0.009) and a nearly two-fold increase in OPN levels after 6 h (LPS: 155 ± 19 pg/ml; placebo: 85 ± 13 pg/ml, p < 0.001). LPS gradually reduced CTX levels (LPS: 0.44 ± 0.4 pg/ml; placebo: 0.59 ± 0.06 pg/ml, p = 0.003), P1NP showed a peak at 4 h (LPS: 89.9 ± 14.7 pg/ml; placebo: 75 ± 9.7 pg/ml, p = 0.028) and circulating OC did not change. The early human response to systemic endotoxemia boosts osteopontin levels and modifies bone biomarkers, indicating a decrease in the lytic activity of osteoclasts, accompanied by an increase in the activity of immature osteoblasts. These changes might present the acute phase response of immune and bone cells to bacterial stimuli in men.

Relation of bone turnover markers to periodontal disease and jaw bone morphology in elderly Japanese subjects

The purpose of this study was to evaluate the relation of bone turnover markers such as bone formation and resorption to periodontal disease and jaw bone morphology in elderly Japanese subjects. We selected 148 subjects for participation in this study. All subjects were aged 77 years. The periodontal examination included the assessment of clinical attachment level (CAL). Biochemical parameters of bone turnover measured included urinary deoxypyridinoline, serum osteocalcin (S-OC), and serum bone-specific alkaline phosphatase. In addition, to evaluate the jawbone, we used the mandibular inferior cortex classification (MIC). Serum osteocalcin had significantly higher (males: P = 0.038, females: P = 0.041) tendency for MIC Class (ANOVA). Multiple linear regression results showed that the number of remaining teeth and S-OC were negatively associated with the percentage of sites with > or =6 mm CAL (R(2) = 0.322, P < 0.001). Coefficients and betas were -0.71, -0.46 (P < 0.001) and -1.11, -0.28 (P = 0.002), respectively. In conclusion, this study suggests that there is a significant relation of bone turnover markers to periodontal disease and jaw bone morphology in elderly Japanese subjects.

The Effect of a Single Infusion of Zoledronic Acid on Early Implant Migration in Total Hip Arthroplasty

Aseptic loosening is the most frequent cause of implant failure in total hip arthroplasty. While a direct link between aseptic loosening and periprosthetic bone loss remains elusive, there is plentiful evidence for a close association with early implant migration. The present trial was primarily designed to evaluate whether a single infusion of 4 mg of zoledronic acid prevented early implant migration in patients with osteonecrosis of the femoral head. Fifty patients were consecutively enrolled to receive either zoledronic acid or saline solution after cementless total hip arthroplasty. Radiographs, biochemical parameters of bone turnover, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at seven weeks, six months, one year, and yearly thereafter. The median follow-up period was 2.8 years. We found a significant subsidence of the stem of up to a mean (and standard deviation) of -1.2 +/- 0.6 mm at two years within the control group, and the cups had a mean medialization of 0.6 +/- 1.0 mm and a mean cranialization of 0.6 +/- 0.8 mm (p < 0.001). Treatment with zoledronic acid effectively minimized the migration of the cups in both the transverse and the vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p < 0.05), while only a trend to decreased subsidence of the stem was detected. Finally, the Harris hip score rapidly increased over time in both treatment groups, although this increase was significantly more pronounced in the zoledronate-treated group than in the control group (analysis of variance, p = 0.008). A single infusion of zoledronic acid shows promise in improving initial fixation of a cementless implant, which may improve the clinical outcome of total hip arthroplasty in patients with osteonecrosis of the femoral head.

Bone histomorphometry and biochemical markers of bone turnover in patients with chronic kidney disease Stages 3 – 5

Precise identification of renal osteodystrophy requires bone histomorphometry. Several markers of bone turnover may be useful to predict classification and severity of renal osteodystrophy, but there are only limited data whether these markers correlate with bone histomorphometry. In 36 patients with chronic kidney disease (CKD) Stage 3/4 and in 96 patients with CKD Stage 5 bone histomorphometry was performed and renal osteodystrophy was classified according to the standardized international nomenclature. Blood samples were taken at the time of bone biopsy, stored and analyzed at the end of the study. Osteitis fibrosa (OF) was the most frequent histomorphometric form, occurred in 47.2% in CKD Stages 3 - 4 and in 61.4% in CKD Stage 5. There was no difference in the frequency of adynamic renal bone disease (ARBD). The correlation coefficients between bone turnover markers and histomorphometric parameters were higher in CKD 5 patients with high bone turnover lesions. The predictive value for high versus low/normal bone turnover status was comparable for alkaline phosphatase (APH), bone alkaline phosphatase (BAP), pyridinoline (Pyd), desoxypyridinoline (Dpyd), tartrat-resistent acid phosphatase (TRAP Vb) and parathyroid hormone (PTH) in CKD Stage 5 patients, but was insufficient for APH and TRAP Vb in CKD Stage 3 - 4 patients. Besides parathyroid hormone, biochemical parameters of bone turnover provide a moderate discrimination and prediction of bone turnover status only in patients with CKD Stage 5. Due to a large variability, they are of limited use in predicting the histomorphometric type of renal osteodystrophy. Bone histology remains necessary for an exact classification of underlying pathology.

Renal Function and Periodontal Disease in Elderly Japanese

Chronic renal failure involves a slow, progressive loss of renal function over months or years. It is possible that periodontal disease and chronic kidney disease might share common risk factors. This study investigated whether a link exists between periodontal disease and chronic renal function in community-dwelling elderly subjects. A total of 145 study subjects, all 77 years of age, participated in this study. A periodontal examination was carried out by trained dentists. Urine was collected over 24 hours, and blood was taken on the morning of the dental exam. The volume of creatinine per 24 hours (Cre_U) and volume of urine per 24 hours were used as urinary markers of kidney function; serum creatinine levels (Cre_S) were used as a blood marker of kidney function. Creatinine clearance per 24 hours was calculated as Cre_U/Cre_S. In addition, biochemical parameters of bone turnover were measured: urinary deoxypyridinoline (U-DPD) as a bone resorption marker and serum osteocalcin (S-OC) as a bone formation marker. Multiple regression analysis was used to evaluate the relationship between the percentage of periodontal sites with > or =6-mm clinical attachment level (% > or =6-mm CAL) and renal function, as well as the relationship between % > or =6-mm CAL and bone metabolism. The % > or =6-mm CAL was used as the dependent variable. The number of remaining teeth, smoking habit, gender, use of interdental brushes or dental floss, volume of urine per 24 hours, and creatinine clearance per 24 hours were independent variables in the first test. In addition, the number of remaining teeth, smoking habits, gender, use of interdental brushes or dental floss, U-DPD, and S-OC were independent variables in the second test. Multiple regression analysis showed that creatinine clearance per 24 hours and S-OC were significantly associated with % > or =6-mm CAL per person. The standardized coefficients were 0.26 (P = 0.015) and -0.27 (P = 0.006), respectively. The % > or =6-mm CAL was significantly associated with renal function and bone metabolism markers. This study suggests that the increased incidence of chronic renal failure that occurs with age might increase the probability of severe periodontal disease in community-dwelling elderly subjects.

Ileum resection is the most predictive factor for osteoporosis in patients with Crohn’s disease

Crohn's disease is associated with a host of factors potentially increasing the risk for osteoporosis and fractures. The aim of our study was to identify the most predictive factors for skeletal pathology in this patients. Using a cross-sectional study design, 146 randomly selected patients with Crohn's disease of variable disease activity who were given standard therapy to control disease activity, including glucocorticoids, and who attended the outpatient clinic of the Gastroenterology Unit on regular follow-up visits were studied. Bone mineral density (BMD) measurements and lateral X-rays of the spine were performed, and biochemical parameters of bone turnover, gonadal hormones and C-reactive protein (CRP) as markers of disease activity were measured in all patients. There were 61 men and 85 women, with a mean age of 43 years and mean disease duration of 20 years. The majority of patients (86%) had been treated with glucocorticoids at some stage during their illness at a median dose of 7.5 mg/day, 43% were currently using these agents and 66% had undergone an intestinal resection. Twenty-one percent of patients had below-normal 25-hydroxy vitamin D levels. Osteoporosis was documented in 26% of patients, predominantly at the femoral neck, but also at the lumbar spine or at both sites; osteopenia was documented in 45% of patients. Prevalence of vertebral and non-vertebral fractures was, respectively, 6% and 12%. Ileum resection was the most predictive factor for osteoporosis: RR 3.84 (CI 1.24-9.77, p=0.018), followed by age: RR 1.05 (CI 1.02-1.08, p<0.001) and current or past glucocorticoid use: RR 1.94 (CI 0.92-4.10, p=0.08). Our data suggest that in patients with Crohn's disease, the risk of osteoporosis is best predicted by a history of ileum resection.

Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting

To study if T-cell activation related to portasystemic shunting causes osteoclast-mediated bone loss through RANKL-dependent pathways. We also investigated if T-cell inhibition using rapamycin would protect against bone loss in rats. Portasystemic shunting was performed in male Sprague-Dawley rats and rapamycin 0.1 mg/kg was administered for 15 wk by gavage. Rats received powderized chow and supplemental feeds to prevent the effects of malnutrition on bone composition. Weight gain and growth was restored after surgery in shunted animals. At termination, biochemical parameters of bone turnover and quantitative bone histology were assessed. Markers of T-cell activation, inflammatory cytokine production, and RANKL-dependent pathways were measured. In addition, the roles of IGF-1 and hypogonadism were investigated. Portasystemic shunting caused low turnover osteoporosis that was RANKL independent. Bone resorbing cytokine levels, including IL-1, IL-6 and TNFalpha, were not increased in serum and TNFalpha and RANKL expression were not upregulated in PBMC. Portasystemic shunting increased the circulating CD8+ T-cell population. Rapamycin decreased the circulating CD8+ T-cell population, increased CD8+ CD25+ T-regulatory cell population and improved all parameters of bone turnover. Osteoporosis caused by portasystemic shunting may be partially ameliorated by rapamycin in the rat model of hepatic osteodystrophy.

Possible association of psoriasis and reduced bone mineral density due to increased TNF-α and IL-6 concentrations

Psoriasis is a chronic erythematosquamous disease affecting about 2-3% of the population. It is generally considered to be a T cell-mediated disorder. Psoriasis is characterized by Th1-type cytokine pattern with the predominant secretion of IL-2, IL-6, IFN-gamma and TNF-alpha. Such cytokine pattern is sufficient in inducing keratinocyte hyperproliferation, a hallmark of psoriasis. It seems that development of psoriatic lesions is mediated by TNF-alpha and proliferation of local T cells is dependent on local TNF-alpha production. IL-6 enhances activation, proliferation and chemotaxis of T cells into psoriatic lesions. It is also a direct keratinocyte mitogen that could directly stimulate keratinocyte proliferation. Data of possible association between psoriasis and reduced bone mineral density (BMD) are limited and therefore, not fully conclusive. The major limitation of two studies reported so far was small sample size. Based on increased concentrations of TNF-alpha and IL-6 in psoriasis we hypothesized that these patients are more prone to osteoporosis than healthy subjects. TNF-alpha enhances bone resorption via stimulating osteoclast development and activity as well as bone formation. On the other hand, IL-6 is also a potent stimulator of bone resorption. Moreover, increased production of TNF-alpha and IL-6 has been found in postmenopausal women with osteoporosis. Several lines of evidence support our hypothesis; higher value of IL-6 was recorded in children with idiopathic osteoporosis than in healthy controls; TNF-alpha knock-out mice do not lose bone after ovariectomy; polymorphism of TNFRSF1B gene which encodes 75 Kd TNF receptor is associated with BMD; treatment with anti-TNF-alpha antibody exert beneficial effect on bone metabolism in patients with rheumatoid arthritis and finally, raloxifene inhibit osteoclast activity by reducing TNF-alpha and IL-6 synthesis. However, our hypothesis raised number of questions. Are increased serum concentrations of TNF-alpha and IL-6 mirrored by increased concentrations of these cytokines on the local level? Furthermore, could other cytokines relevant in the pathogenesis of the psoriasis, first of all IFN-gamma, modulate the risk of osteoporosis? Thus, a large prospective, case-control study with the data on BMD, biochemical parameters of bone turnover and fractures have to be done to test our hypothesis.

Characterization of the pharmacologic profile of a standardized soy extract in the ovariectomized rat model of menopause: effects on bone, uterus, and lipid profile

This study was aimed to assess the effect of a standardized soy extract (SSE, Soyselect) in the ovariectomized rat model of menopause. Ovariectomized rats were treated for 6 weeks with the soy extract (50 or 100 mg/kg/day - PO), vehicle (distilled water), or 17beta-estradiol (0.5 mg/kg/day - PO). Tissue-specific estrogen agonist effects were examined using the endpoints bone mineral density, biochemical parameters of bone turnover, modulation of cytokines involved in the bone remodeling, uterine weight, uterine histology, uterine hormone receptor status, and serum lipid level. The SSE produced a bone-sparing effect associated with a slowing down in the increased bone turnover observed after ovariectomy (as indicated by measurements of serum osteocalcin levels and excretion ratio of deoxypyridinoline); changes in serum interleukin-6 levels observed after SSE suggested that this bone-sparing effect could be partly attributed to the modulation of osteoclastogenesis induced by interleukin-6. Remarkably, organ weight data and histopathologic analysis did not show any stimulatory activity of the SSE on the uterus. Immunohistochemical analysis showed a significant down-regulation of estrogen receptor-alpha (ERalpha) in uterine epithelium after 17beta-estradiol treatment, but not after treatment with the SSE; no significant differences among groups were observed in ER-alpha uterine stromal levels. After treatment with 17beta-estradiol, estrogen receptor-beta (ER-beta) expression was not modulated in the stroma or epithelium, whereas the SSE induced an up-regulation of ER-beta stromal expression. Collectively, these results suggest that the lack of stimulatory activity on the uterine epithelium using soy treatment could be due to a negligible stimulatory activity on estrogen receptor-alpha and/or to the enhanced expression observed in stromal ER-beta, the latter being considered as a negative modulator of ERalpha-mediated uterine proliferation. 17beta-estradiol, but not the SSE, down-regulated uterine epithelial progesterone receptor (PR), compared with ovariectomized rats. In the stromal compartment, progesterone receptor expression was fully up-regulated by 17beta-estradiol treatment and, to a lesser extent, by SSE treatment. The minor increase in lipid levels induced by ovariectomy was not affected by SSE administration. Finally, the lack of stimulatory activity on uterus was also confirmed in an immature female rat model. The results of this study demonstrated that the tested extract has an interesting profile of tissue-specific response, in that it is efficacious in preventing experimental osteoporosis without causing stimulation in uterus at doses that are effective in bone.

Absorption of the oral bisphosphonate alendronate in osteoporotic patients with Crohn’s disease

The absorption of bisphosphonates from the gut is poor. The question arises whether the absorption of alendronate, and thus its bioavailability, is further altered by the local inflammatory process in patients with Crohn's disease, thereby potentially affecting clinical outcome when used in the treatment of osteoporosis. To address this question, urinary excretion of alendronate was evaluated 3 months and 6 months after start of treatment with oral alendronate at a dose of 10 mg/day in 19 osteoporotic patients with stable Crohn's disease, 12 of whom had an intestinal resection. Biochemical parameters of bone turnover and BMD were also measured at start and at 6 months. Thirteen patients had been previously treated with glucocorticoids and five were currently using them. The average 24-h urinary excretion of alendronate was 0.5-0.6% of the dose administered, a figure comparable to that reported for osteoporotic patients without gut pathology. There was a significant decrease from baseline in urine N-telopeptides of collagen cross-links (NTx)/creatinine (60%) associated with an increase in lumbar spine BMD of already 2% after 6 months of treatment. Our data suggest that in patients with Crohn's disease, alendronate is adequately absorbed from the intestine and retained in the skeleton. This adequacy is confirmed by appropriate suppression of bone resorption and increase in lumbar spine BMD. These data hold significant implications for the clinical management of patients with Crohn's disease and osteoporosis.

A two‐year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis

To explore early changes and predictors of bone mass in children with juvenile idiopathic arthritis (JIA) in order to identify patients who will develop bone mass reductions. We conducted a prospective cohort study of 108 children with early JIA (ages 6-18 years; mean disease duration 19.3 months) who were individually matched with 108 healthy children for age, sex, race, and county of residence. Bone mass and changes in total body, spine, femur, and forearm bone mineral density and bone mineral content (BMC), body composition, growth, and biochemical parameters of bone turnover were examined at baseline and at followup a mean of 24 months later. Low bone mass was defined as a Z score >1 SD below the reference population. Of the 200 children evaluated at followup, the 100 healthy children had greater gains in total body BMC (P = 0.035), distal radius BMC (P < 0.001), and total body lean mass (P < 0.001) than did the 100 JIA patients. Low or very low total body BMC was observed in 24% of the patients and 12% of the healthy children. Bone formation, bone resorption, and weight-bearing activities were reduced in the patients compared with the healthy children. Multiple regression analysis showed that in patients with JIA, serum bone-specific alkaline phosphatase, serum C-telopeptide of type I collagen, and weight-bearing activities were independent predictors of changes in total body BMC. Total body BMC was lower in patients with polyarticular onset than in those with oligoarticular disease onset. Patients with JIA have moderate reductions in bone mass gains, bone turnover, and total body lean mass early in the disease course.

Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study

The aim of this study was to explore the effect of long-term cross-sex hormonal treatment on cortical and trabecular bone mineral density and main biochemical parameters of bone metabolism in transsexuals. Twenty-four male-to-female (M-F) transsexuals and 15 female-to-male (F-M) transsexuals treated with either an antiandrogen in combination with an estrogen or parenteral testosterone were included in this cross-sectional study. BMD was measured by DXA at distal tibial diaphysis (TDIA) and epiphysis (TEPI), lumbar spine (LS), total hip (HIP) and subregions, and whole body (WB) and Z-scores determined for both the genetic and the phenotypic gender. Biochemical parameters of bone turnover, insulin-like growth factor-1 (IGF-1) and sex hormone levels were measured in all patients. M-F transsexuals were significantly older, taller and heavier than F-M transsexuals. They were treated by cross-sex hormones during a median of 12.5 years before inclusion. As compared with female age-matched controls, they showed a significantly higher median Z-score at TDIA and WB (1.7+/-1.0 and 1.8+/-1.1, P < 0.01) only. Based on the WHO definition, five (who did not comply with cross-sex hormone therapy) had osteoporosis. F-M transsexuals were treated by cross-sex hormones during a median of 7.6 years. They had significantly higher median Z-scores at TEPI, TDIA and WB compared with female age-matched controls (+0.9+/-0.2 SD, +1.0+/-0.4 SD and +1.4+/-0.3 SD, respectively, P < 0.0001 for all) and reached normal male levels except at TEPI. They had significantly higher testosterone and IGF-1 levels (p < 0.001) than M-F transsexuals. We conclude that in M-F transsexuals, BMD is preserved over a median of 12.5 years under antiandrogen and estrogen combination therapy, while in F-M transsexuals BMD is preserved or, at sites rich in cortical bone, is increased to normal male levels under a median of 7.6 years of androgen treatment in this cross sectional study. IGF-1 could play a role in the mediation of the effect of androgens on bone in F-M transsexuals.