Bone mineral density of the spine and radius shaft in children with X-linked hypophosphatemic rickets (XLH)

X-linked hypophosphatemic rickets (XLH) is characterized by inadequate skeletal mineralization. The bone mineral density (BMD) of the radius shaft and the lumbar spine was determined in 13 children with XLH. Ten patients were on treatment, whereas three patients had discontinued treatment 20–32 months prior to this study. Two of them had radiological evidence of rickets.The radius shaft BMD was significantly diminished: Z score was −1.33 ± 0.89 (P < 0.001), while the BMD of lumbar spine was significantly augmented (Z score + 1.95 ± 1.17, P < 0.001). A positive correlation was found between the Z scores for the BMD of the radius shaft and spine. The two patients with overt rickets had lower radius shaft BMD values and a lesser increment of BMD of the spine. The BMD deficit of cortical bone may be related to the lack of efficacy of the treatment and/or to an intrinsic defect of the bone on this disease. On the other hand, the augmented BMD of the lumbar spine might reflect the overabundance of partially mineralized osteoid.The determination of the BMD of the radius shaft by SPA was a sensitive method for detecting abnormalities of the bone mass in XLH patients under treatment without radiological signs of rickets.     

Effects of Bisphosphonates on Osteoporosis Induced by Duchenne Muscular Dystrophy: A Prospective Study

Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD.Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated.Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group (P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline).Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol.Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid     

Bone loss in response to long-term glucocorticoid therapy

A number of studies have shown that an excess of glucocorticoids induces osteoporosis, but the mechanism(s) and the time course of the reduction of bone mass remain uncertain. In order to clarify this issue we carried out a longitudinal clinical and histomorphometric study of patients requiring long-term glucocorticoid treatment.In 23 patients (9 men, 10 post- and 4 premenopausal women) biochemical and bone histomorphometric investigations were carried out before and during treatment with 10–25 mg/day of prednisone. Histomorphometric analysis of bone biopsies of the iliac crest showed that the decrease of TBV (up to −27%, P < 0.001) occurs predominantly within the first 5–7 months of treatment; during the subsequent stages, which include observations after 12 months of treatment, only minor changes were observed. Therefore trabecular bone loss can be satisfactorily described by a negative exponential function. None of the other histomorphometric parameters (osteoid surfaces, resorption surfaces, etc.) showed significant changes. However, the histological features of the bone biopsies during steroid therapy, showing a virtual lack of osteoblastic activity, ruled out an increase of bone resorption. Moreover, the dynamic study of the bone formation by double tetracycline labelling showed, in a small subgroup of patients, a decrease of the apposition rates (from 0.763 ± 0.053 to 0.305 ± 0.074 μ/day (mean ± SE) after treatment).No significant changes, at any time during steroid treatment, were observed in serum alkaline phosphatase, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone or urinary calcium excretion. Serum calcium increased significantly within the first 1–2 months of therapy and then it returned to baseline. Urinary hydroxyproline excretion decreased significantly within the first 1–2 months and continued to fall throughout the treatment.Thus, both biochemical and histological findings suggest that long-term glucocorticoid therapy causes a reduction of bone turnover, that the bone loss occurs predominantly within the first 6 months of treatment and that patients with lower bone mass have a lower rate of bone loss.     

A 1-year case-control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab

The goal of the present study was to record changes in bone mineral density (BMD) and markers of bone turnover in patients with rheumatoid arthritis (RA) who were treated with methotrexate combined (or not combined) with infliximab. Included were 90 patients with RA who required anti-TNF-α therapy with infliximab because of persistent active disease despite treatment with methotrexate. The historical control group included 99 patients with RA who were treated with methotrexate at a time when anti-TNF-α treatment was not yet available. Lumbar and femoral neck BMD was measured using dual energy X-ray absorptiometry at baseline and 1 year later. Osteocalcin, C-terminal cross-linked telopeptide of type I collagen, parathyroid hormone and 25-hydroxycholecalciferol were measured in plasma at baseline and 1 year later. At 1 year BMD had decreased in the control group at spine (P < 0.01) and femoral neck (P < 0.001). In contrast, BMD at spine and femoral neck did not change after 1 year of infliximab treatment. At the same time point, no change in bone remodelling markers was observed. No association was observed between clinical response and changes in BMD, indicating that even those who did not respond clinically did not lose bone over a 1-year period. These data confirm the BMD decrease observed in RA patients treated with methotrexate alone. This bone loss was prevented by infliximab therapy. Importantly, this beneficial effect was also observed in apparent nonresponders.     

A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women

Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1‐year follow‐up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6‐month exercise‐based weight loss program and returned for follow‐up at 18 months. Dual‐energy X‐ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m². They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow‐up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (?1.7 ± 3.5%; P = 0.002) and hip (?0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C‐terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (?0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: ?3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone‐deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.     

Efectos del tratamiento con ácido zoledrónico en pacientes adultos con osteogénesis imperfecta

Background and objectiveOsteogenesis imperfecta (OI) is a genetic disorder that results in bone fragility. Several studies have demonstrated the effectiveness of bisphosphonate therapy. The aim of this study was to evaluate the effects of intravenous zoledronic acid on bone mineral density (BMD) and biochemical markers of bone turnover in adults with OI.Material and methodsWe carried out a prospective non-randomized study in patients with osteoporosis or severe osteopenia (T score <?2) related to OI and intolerance or contraindication to oral bisphosphonates. The patients were treated with a zoledronic acid infusion every 6 months. Densitometry was carried out annually. Calcium (Ca), phosphate (P), intact parathormone (PTH), 25 hydroxyvitamin D and biochemical markers of bone turnover [bone alkaline phosphatase (BAP), beta-cross-laps (CTX) and urinary deoxypyridoxine (DOP)] were measured every year. Adverse events and new fractures were registered.ResultsTen patients (2 men and 8 women) were treated. Treatment increased BMD measured in the lumbar spine after 24 (0.738±0.141 vs 0.788±0.144 g/cm²; p=0.048) and 36 months (0.720±0.139 vs 0.820±0.128; p=0.01). Significant increases in BMD were also observed after 24 months in the femoral neck (0.677±0.121 vs 0.703±0.122 g/cm²; p<0.016). Serum Ca, P, BAP and CTX concentrations remained unchanged. PTH concentrations increased and vitamin D concentrations decreased after 36 months of treatment. DOP excretion decreased significantly after 24 months. Seven patients had mild influenza-like symptoms occurring within the first 24 h after the first infusion. No severe adverse events were observed. None of the patients had new fractures.ConclusionZoledronic acid seems to be a safe and effective treatment option in adults with osteoporosis related to OI.     

Effects of Bisphosphonates on Bone of Osteoporotic Men With Different Androgen Levels: A Case-Control Study

ObjectiveOsteoporosis in men has been neglected despite its association with disability and mortality. We evaluated the effect of bisphosphonates (BPs) on bone mineral density (BMD) and bone turnover biomarkers of osteoporotic men with different androgen levels.MethodsThis case-control study included 136 osteoporotic men who were divided into normal group (n = 75) and hypogonadism group (n = 61) (patients treated with testosterone were excluded) according to their serum testosterone levels (cutoff value, 350 ng/dL). BMD, serum testosterone, total alkaline phosphatase, and cross-linked C-telopeptide of type I collagen were detected. The relationship between testosterone levels and BMD at baseline was evaluated. All patients were treated with BPs for 2 years. We compared the effects of BPs on BMD and bone turnover biomarkers between the 2 groups.ResultsAt baseline, there were no significant differences in BMD and bone turnover biomarkers between the 2 groups. Testosterone levels were positively correlated with BMD in the hypogonadism group. After treatment, the lumbar BMD increased by 7.65% ± 1.54% and 7.47% ± 1.88% in normal and hypogonadism groups, respectively (both P < .01 vs baseline) and hip BMD increased without significant differences between the 2 groups. Serum cross-linked C-telopeptide of type I collagen and alkaline phosphatase levels decreased without significant differences between the 2 groups (all P < .01 vs baseline).ConclusionTestosterone level is positively correlated with BMD in men with hypogonadism. In osteoporotic men, BPs significantly increase spine and hip BMD and decrease bone resorption. The efficacy of BPs is similar in men with or without hypogonadism.     

Correlation Between Bone Markers and Bone Mineral Density in Postmenopausal Women with Osteoporosis

ObjectiveTo study the relationship between bone markers and bone mineral density (BMD) in an effort to identify their utility in postmenopausal women with osteoporosis.MethodsEighty-two consecutive postmenopausal women with untreated osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual-energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) and bone resorption (urinary free deoxypyridinoline) were measured in all patients. Patients with low serum vitamin D levels, secondary osteoporosis, or clinically significant systemic disease were excluded from the study. The patients were classified on the basis of BMD of the lumbar spine into the following 3 groups: mild (n = 23) (T score -2.5 through -3), moderate (n = 42) (T score -3.1 through -4), or severe (n = 17) (T score ≤-4.1) osteoporosis. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < .05 being considered significant.ResultsSerum osteocalcin was significantly different among the 3 study groups (4.1 ± 2.7, 4.5 ± 3.1, and 6.7 ± 5.6 ng/mL, respectively; P = .0349) and had a significant negative correlation with BMD (r² = -0.0779; P = .0168). Other bone markers such as bone-specific alkaline phosphatase and urinary free deoxypyridinoline did not correlate with the underlying BMD.ConclusionIn our study, osteocalcin was significantly correlated with BMD in postmenopausal women with osteoporosis. Other bone markers did not correlate with BMD. Further large-scale population data and analyses are needed to confirm these findings. (Endocr Pract. 2008;14:1102-1107)     

Bone Mineral Density in Pituitary Stalk Interruption Syndrome: The Role of Insulin-Like Growth Factor-1 and Testosterone at Different Skeletal Sites

ObjectiveThis study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT).MethodsMale patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites.ResultsFifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009).ConclusionCollectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non–recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.     

Trabecular Bone Score Change Differs with Regard to 25(OH)D Levels in Patients Treated for Adult-Onset Growth Hormone Deficiency

Objective: Vitamin D is important in bone health. However, potential relationships of concomitant vitamin D deficiency with growth hormone deficiency (GHD) and the possibility that vitamin D inadequacy may alter the skeletal effects of growth hormone (GH) replacement therapy have not been adequately evaluated.Methods: A prospective study was conducted in adult-onset GHD patients treated with recombinant human GH (rhGH) for 2 years. Trabecular bone score (TBS), lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and 25-hydroxyvitamin D (25(OH)D) levels were assessed at baseline and 24 months. The study cohort was divided based on 25(OH)D levels into 2 groups with the cutoff defined as the 50^th percentile at each follow-up time point.Results: Fifty-seven patients (29 males/28 females, mean age 34.4 years) were studied. After 24 months of GH replacement, LS BMD increased by 7.6% and TH BMD increased by 4.5% (both P<.05), with no difference according to 25(OH)D levels. TBS increased (+1.39 ± 3.6%) in those whose 25(OH)D was above the 50^th percentile but decreased (-1.36 ± 5.6%, P<.05) in the cohort below the 50^th percentile of 25(OH)D. Positive correlations were observed between baseline levels of IGF-1 and 25(OH)D (R = 0.37, P<.001) and between 24-month 25(OH)D and TBS (R = 0.25, P<.05).Conclusion: A differential effect of GH on TBS change was observed; TBS increased only in the cohort with 25(OH)D above the 50^th percentile. Vitamin D sufficiency may be required to obtain optimal effects of GH treatment on bone quality, as assessed by TBS, in GHD adults.Abbreviations:AO-GHD = adult-onset GHDBMD = bone mineral densityBMI = body mass indexCa = calciumCTx = carboxyterminal collagen crosslinksCV = coefficient of variationDXA = dual energy X-ray absorptiometryECLIA = enzyme-labeled chemiluminescent immunometric assayGH = growth hormoneGHD = growth hormone deficiencyIGF-1 = insulin-like growth factor 1LS BMD = lumbar spine BMDOC = osteocalcin25(OH)D = 25-hydroxyvitamin DP = phosphorusPTH = parathyroid hormonerhGH = recombinant human GHTBS = trabecular bone scoreTH BMD = total hip BMD     

Prevention of Bone Loss After Withdrawal of Tamoxifen

ObjectiveTamoxifen has antiestrogenic effects in the breast and estrogenlike activity in the skeletons of post-menopausal women. We hypothesized that post-menopausal women with breast cancer would experience a rapid decline in bone mineral density (BMD) after stopping tamoxifen, similar to that seen with estrogen withdrawal. The objective of this study was to assess, in a randomized, double-blind, placebo-controlled trial, whether administration of alendronate (70 mg weekly) would prevent bone loss associated with tamoxifen discontinuation.MethodsPostmenopausal women with breast cancer were randomly assigned to receive alendronate or placebo for 1 year within 3 months after withdrawal of tamoxifen therapy. We initiated a randomized, double-blind, placebo-controlled trial of alendronate (70 mg weekly) in an effort to prevent bone loss associated with discontinuation of tamoxifen therapy. Patients treated with aromatase inhibitors were excluded from the study. BMD at the spine, hip, and forearm was measured at baseline and at 12 months. Analyses employed repeated-measures analysis of variance.ResultsPatient accrual was considerably limited by the substantial increase in use of aromatase inhibitors during the enrollment period. The study patients (N = 11) had similar baseline BMD T-scores in the alendronate (n = 6) and placebo (n = 5) subgroups. After 1 year, tamoxifen withdrawal was associated with a significant decline in BMD at the femoral neck, which appeared to be prevented by weekly administration of alendronate (-5.2% versus 0.1%; P = .02). Levels of urinary N-telopeptide, a marker of bone turnover, increased by 48% in study subjects in the placebo group (P < .01), whereas weekly alendronate treatment was associated with a 52% decline (P < .01) in this bone resorption marker.ConclusionDifferences in BMD and bone turnover were evident despite the small sample size. These data suggest that postmenopausal women with breast cancer completing tamoxifen therapy warrant an evaluation of their skeletal health and that bisphosphonate therapy may be useful in preventing bone loss associated with discontinuation of tamoxifen. (Endocr Pract. 2008;14:162-167)     

Increased Bone Mineral Density in Male Patients With Idiopathic Hypogonadotropic Hypogonadism Who Undergo Sex Hormone Therapy: Findings From Cross-Sectional and Longitudinal Studies

ObjectiveThis retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH).MethodsIn the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD.ResultsOur cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05).ConclusionSex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck.     

Osteoporosis in ankylosing spondylitis - prevalence, risk factors and methods of assessment

Introduction

Osteoporosis can be a complication of ankylosing spondylitis (AS), but diagnosing spinal osteoporosis can be difficult since pathologic new bone formation interferes with the assessment of the bone mineral density (BMD). The aims of the current study were to investigate prevalence and risk factors for reduced BMD in a Swedish cohort of AS patients, and to examine how progressive ankylosis influences BMD with the use of dual-energy x-ray absorptiometry (DXA) of the lumbar spine in different projections.

Methods

Methods of assessment were questionnaires, back mobility tests, blood samples, lateral spine radiographs for syndesmophyte grading (mSASSS), DXA of the hip, radius and lumbar spine in anteroposterior (AP) and lateral projections with estimation of volumetric BMD (vBMD).

Results

AS patients (modified New York criteria), 87 women and 117 men, mean age 50 ± 13 years and disease duration 15 ± 11 years were included. According to World Health Organization (WHO) criteria 21% osteoporosis and 44% osteopenia was diagnosed in patients > = 50 years. Under age 50 BMD below expected range for age was found in 5%. Interestingly lateral lumbar DXA showed significantly lower BMD and revealed significantly more cases with osteoporosis as compared with AP DXA. Lumbar vBMD was not different between sexes, but women had significantly more lumbar osteoporosis measured with AP DXA (P < 0.001). Men had significantly higher mSASSS (P < 0.001). Low BMD was associated with high age, disease duration, mSASSS, Bath Ankylosing Spondylitis Metrology Index (BASMI), inflammatory parameters and low body mass index (BMI). Increasing mSASSS correlated significantly with decreasing lateral and volumetric lumbar BMD, while AP lumbar BMD showed tendency to increase.

Conclusions

Osteoporosis and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting osteoporosis and are less affected by syndesmophyte formation.     

Axial BMD in Diabetic and Nondiabetic Southeast Asians with HIP Fractures: Do Race and Body Mass Index Matter?

Objective: Obesity is less prevalent in Asian subjects with type 2 diabetes mellitus (T2DM) in contrast to Caucasians. Whether higher axial bone mineral density (BMD) often reported in T2DM is independent of body mass index (BMI) has not been clearly shown. BMD characterization in T2DM patients with hip fractures has also not been performed. We compared the BMD of Asian diabetic and nondiabetic patients with new hip fractures and explored how BMD was influenced by BMI.Methods: We included 255 diabetic and 148 nondiabetic patients. BMD adjusted for age; BMI; race; sex; renal function; and use of statins, proton pump inhibitors, steroids, anticonvulsants, and calcium and/or vitamin D supplements were compared between the groups. We were particularly interested in the BMD comparison between underweight diabetics and nondiabetics with hip fractures.Results: The presence of T2DM was associated with higher BMD (g/cm²) at the femoral neck (0.527 ± 0.103 vs. 0.491 ± 0.102, P<.01) and lumbar spine [LS] (0.798 ± 0.147 vs. 0.723 ± 0.156, P<.01). This association persisted after adjustment for multiple confounding variables including BMI. The age-, BMI-, and sex-adjusted LS BMD was higher in underweight (BMI <18.5 kg/m²) diabetics compared to similar weight nondiabetics (0.733 ± 0.126 vs. 0.649 ± 0.131 g/cm², P = .014).Conclusion: T2DM is independently associated with higher axial BMD in patients with new hip fractures. The finding of higher BMD even in underweight diabetics with hip fractures compared to their nondiabetic counterparts suggests that higher BMD in subjects with T2DM is not due to higher BMI.Abbreviations:BMD = bone mineral densityBMI = body mass indexCV = coefficient of variationDXA = dual-energy X-ray absorptiometryHbA1c = glycated hemoglobinIGF-1 = insulin growth factor-1LS = lumbar spine25(OH)D = 25-hydroxyvitamin DT2DM = type 2 diabetes mellitus     

Association of ESR1 and C6orf97 gene polymorphism with osteoporosis in postmenopausal women

The estrogen receptor 1 (ESR1) and Chromosome 6 Open Reading Frame 97 (C6orf97) gene polymorphisms were earlier reported to be associated with osteoporosis in the European cohort. The aim of this study was to investigate the association of four single nucleotide polymorphisms (SNP) with bone mineral density (BMD), fracture, vertebral fracture, bone turnover or 25-hydroxyvitamin D [25(OH)D] in 1,753 randomly selected postmenopausal women in China. Vertebral fracture, BMD of lumbar spine (2–4), femoral neck and total hip were measured respectively. Serum N-terminal procollagen of type 1 collagen (P1NP), β-isomerized type I collagen C-telopeptide breakdown products (β-CTX) and 25(OH)D3 were also determined. Binary logistic regression revealed significant associations between fracture risk with rs1999805 (P = 0.041, OR 1.633, 95 %CI 1.020–2.616) and rs6929137 (P = 0.005, OR 1.932, 95 %CI 1.226–3.045) in recessive model. Significant association was also observed between vertebral fracture risk and rs1038304 (P = 0.039, OR 0.549, 95 %CI 0.311–0.969) in recessive model. Liner regression analyses showed that only the CC group of rs4870044 was significantly associated with total hip in dominant model (P = 0.034). Our findings suggest that ESR1 and C6orf97 gene polymorphism is associated with fracture and vertebral fracture risk in Chinese postmenopausal women.     

Zoledronic Acid Treatment of Osteoporosis: Effects in Men

ObjectiveTo study changes in bone mineral density (BMD) and a bone resorption marker in elderly men who received off-label zoledronic acid for osteoporosis treatment.MethodsWe conducted a retrospective review of medical records of 50 male veterans who had received at least one 4-mg intravenous infusion of zoledronic acid and had BMD measurements at 2 of 3 skeletal sites both before the infusion and at a mean of 2.2 years after the infusion. Patients were classified into those who had never received bisphosphonate therapy versus those who had previously received such treatment.ResultsIn our study population, 66% of patients had been prescribed orally administered bisphosphonates or intravenously administered pamidronate before receiving zoledronic acid. Larger increases in spine BMD (6.7% versus 3.4% [P < .05]; per year: 2.8% versus 1.2% [P < .01]) and total hip BMD (3.2% versus 0.1% [P < .03]; per year: 1.3% versus 0.02% [P < .02]) occurred after infusion of zoledronic acid in bisphosphonate-naïve patients in comparison with those who had previous bisphosphonate exposure. In addition, 26 of 50 patients (52%) had suppressed urinary N-terminal telopeptide of cross-linked collagen type I (NTx) (a bone turnover marker) at 12 months, and 5 men had NTx suppression for 24 months after infusion.ConclusionOur data suggest that 4 mg of intravenously administered zoledronic acid is an effective treatment for increasing BMD in a “real-world” population of men with osteoporosis. The prolonged suppression of urinary NTx after zoledronic acid infusion raises the question of whether this treatment could be given less frequently than every year. The changes seen in BMD during a mean period of 2 years were similar to those reported in clinical studies with alendronate therapy in men and zoledronic acid treatment in women. (Endocr Pract. 2010;16:960-967)     

Bone Mineral Density In Patients With Addison Disease On Replacement Therapy With Prednisolone

Objective: In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement.Methods: Forty-one consecutive patients (31 males, age &lsqb;mean ± SD] 50.9 ± 13.0 years), receiving prednisolone (hydrocortisone equivalent &lsqb;HCE] 13.0 ± 3.0 mg/m²) for 104 ± 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677).Results: Among males, BMD Z-scores (mean &lsqb;95% confidence interval {CI}]) at lumbar spine (-0.42 &lsqb;-0.80, -0.04]), femoral neck (-0.50 &lsqb;-0.95, -0.06]) and total hip (-0.58 &lsqb;-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score ≤-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD.Conclusions: Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites.Abbreviations:ACTH = adrenocorticotropic hormoneBAP = bone-specific alkaline phosphataseBMD = bone mineral densityBMI = body mass indexCI = confidence intervalHCE = hydrocortisone equivalent25 (OH) D3 = 25-hydroxyvitamin D3PAI = primary adrenal insufficiency     

Treatment of multiple myeloma with nasal spray calcitonin: a histomorphometric and biochemical study

To evaluate the effect of calcitonin on the bone lesions of multiple myeloma, we studied 11 patients treated for 3 months with salmon calcitonin in nasal spray (200 IU) and 500 mg of elemental calcium/day. Pre- and post-treatment biochemical and histomorphometric parameters were compared to those of 12 patients treated for the same time with 500 mg elemental calcium alone. Both groups received the same hematological treatment.In the group treated with calcitonin there was a significant increase (P < 0.01) in trabecular bone volume, cortical thickness, osteoid volume and osteoid seam thickness index and the osteoclast resorption surface fell significantly (P < 0.01). There was also a decline (P < 0.001) in corrected serum calcium and OHP/Cr, which accounts for the diminished bone resorption. The group not treated with calcitonin showed only significant changes in OHP/Cr which increase (P < 0.05).Calcitonin was perfectly tolerated by all patients and our results show it to be useful in the treatment of bone lesions of multiple myeloma.     

Differences in Clinical Manifestations and Tumor Features Between Metastatic Pheochromocytoma/Paraganglioma Patients With and Without Germline SDHB Mutation

ObjectiveTo compare metastatic pheochromocytoma/paraganglioma (MPP) patients with germline SDHB mutations (SDHB MPP) and without SDHB mutations (non-SDHB MPP) in terms of baseline clinical manifestations, tumor characteristics, and outcomes.MethodsClinical data were retrospectively reviewed in 101 MPP patients, including 34 SDHB MPP patients and 61 non-SDHB MPP patients.ResultsSDHB MPP patients presented at a younger age at onset, diagnosis, or metastasis (25 ± 16 vs 36 ± 14, 28 ± 17 vs 38 ± 15, and 31 ± 17 vs 44 ± 14 years old, respectively, P < .01 for all) than non-SDHB patients. Compared with their non-SDHB counterparts, SDHB patients were more likely to have paragangliomas (83% vs 47%, P < .05), synchronous metastases (44% vs 23%, P < .05), bone metastases (80% vs 48%, P < .01), and a shorter progression-free survival (3 years vs 5 years, P < .01). The Ki-67 index was higher in SDHB tumors (P < .05). The 5- and 10-year survival rates were 79% and 74%, respectively, in all patients. Seventeen patients died from MPP, and the time from metastasis to death in patients who had received systemic therapy was significantly longer than in those who had not (3.1 ± 1.5 vs 1.4 ± 0.7 years, P < .01).ConclusionCompared with MPP patients without SDHB mutations, MPP patients with SDHB mutations were younger at onset, diagnosis, or metastasis; had a higher incidence of synchronous metastases, higher ratio of paraganglioma, and higher Ki-67 index; had a shorter postoperative progression-free survival; and were more likely to develop bone metastasis or sole liver metastasis. Our results suggest that patients with SDHB mutations should be identified early and monitored regularly to achieve optimal clinical outcomes.     

Melanopsin-expressing retinal ganglion cell loss and behavioral analysis in the Thy1-CFP-DBA/2J mouse model of glaucoma

In this study,the role of melanopsin-expressing retinal ganglion cells(mRGCs) in the glaucoma-induced depressive behavioral response pattern was investigated.The CFP-D2 transgenic glaucoma animal model from five age groups was used in this study.Immunohistochemical labeling,quantitative analysis of mRGC morphology,open field test(OFT),and statistical analysis were used.In comparison with C57 BL/6 mice,the age-matched CFP-D2 mice had significantly elevated intraocular pressure(IOP).We observed parallel morphological changes in the retina,including a reduction in the density of cyan fluorescent protein(CFP) expressing cells(cells mm 2 at 2 months of age,1309±26;14 months,878±30,P<0.001),mRGCs(2 months,48±3;14 months,19±4,P<0.001),Brn3b-expressing RGCs(2 months,1283±80;14 months,950±31,P<0.001),Brn-3b expressing mRGCs(5 months,50.17%±5.5%;14 months,12.61%±3.8%,P<0.001),and reduction in the dendritic field size of mRGCs(mm2 at 2 months,0.077±0.015;14 months,0.065±0.015,P<0.05).CFP-D2 mice had hyperactive locomotor activity patterns based on OFT findings of the total distance traveled,number of entries into the center,and time spent in the center of the testing apparatus.The glaucoma induced hyperactive response pattern could be associated with dysfunctional mRGCs,most likely Brn-3b-positive mRGCs in CFP-D2 mice.