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AIM: We aimed to improve bone health management of children with Cerebral Palsy (CP) by reviewing studies investigating bisphosphonate therapy in children with CP and other types of secondary osteoporosis.METHODS: We included trials on bisphosphonate treatment reporting any direct bone measurement or fracture outcome. All studies of patients with CP were included. We also included all controlled trials of children with secondary bone fragility as well as observational studies with ≥20 participants or at least three years of follow-up. Studies were assessed according to PRISMA guidelines using the RoB2-tool and the Newcastle-Ottawa Scale.RESULTS: We reviewed 1,004 studies and found 38 eligible. Some studies were sufficiently homogeneous to include in a meta-analysis and we found a one-year effect on lumbar spine bone mineral density (BMD) Z-score of +0.65 after oral and +1.21 after intravenous bisphosphonates in children with secondary osteoporosis. Further, data on adverse events and post-treatment follow-up were reviewed. Limitations were heterogeneity and small size of the included studies.CONCLUSION: Meta-analysis consistently showed significant BMD increases with bisphosphonates in children with secondary osteoporosis. Direct evidence of the effect of bisphosphonates on reducing fractures is lacking. We found no reports of long-term adverse events yet longer studies are needed.

Summary: In patients with non-metastatic prostate cancer, treated with radiation therapy and androgen deprivation therapy for 3 years and DMAB on average for 5 years, BMD was in the normal or osteopenic range. Discontinuation of DMAB led to a bone loss of 2–5%. In men with osteopenia, the bone loss was prevented by zoledronate. Purpose: Patients with prostate cancer receiving androgen deprivation therapy (ADT) are treated with denosumab (DMAB) to prevent fractures and preserve bone mass. We wanted to investigate the change in BMD in men with non-metastatic prostate cancer discontinuing DMAB. Methods: We conducted a retrospective cohort study based on medical records from patients referred to the Department of Endocrinology from the Department of Urology, Aarhus University Hospital between June 1, 2018, and June 1, 2021. We retrieved information on biochemistry and DXA performed 0–6 months after the last DMAB injection and a second DXA performed approximately 12 months after the first. In case of a BMD T-score ≤ − 1 at the lumbar spine or total hip at the first DXA, the patients were treated with zoledronate. The primary endpoint was change in lumbar spine BMD. Results: We included 50 patients with non-metastatic prostate cancer. The mean DMAB treatment duration was 5 ± 0.1 years. Among the patients treated with zoledronate (n = 9), BMD was maintained at the spine and femoral neck after a mean of 16 months. We found a significant decrease in BMD; − 4.9 ± 4.2%, − 1.9 ± 3.5%, and − 2.4 ± 3.6% at the spine, total hip, and femoral neck between the first and second DXA in the patients not treated with zoledronate (n = 24) (p ≤ 0.01 for all). One patient who did not receive ZOL sustained multiple fragility vertebral fractures after DMAB discontinuation. Conclusion: In men with non-metastatic prostate cancer, discontinuation of DMAB after stopping ADT led to an average bone loss of 2–5%. Zoledronate prevented bone loss in men with osteopenia.

UNLABELLED: In this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by denosumab for a further 24 months, resulted in early and sustained risk reduction for major fracture categories, associated with large gains in bone mineral density. INTRODUCTION: In the multinational FRAME phase 3 trial of romosozumab in postmenopausal women with osteoporosis, marked differences between clinical and non-vertebral fracture outcomes were observed among patients from Central and Southern America versus rest of world. This post hoc analysis assessed romosozumab efficacy and safety in European patients enrolled in the FRAME trial and extension study. METHODS: In FRAME (NCT01575834), patients were randomised 1:1 to romosozumab 210 mg or placebo monthly (QM) for 12 months, followed by open-label denosumab 60 mg Q6M to month 36, including a 12-month extension study. We report incidence of major fracture outcomes, bone mineral density (BMD) change from baseline and safety for European patients enrolled in FRAME. RESULTS: In FRAME, 3013/7180 (41.96%) patients were European; 1494 received romosozumab and 1519 received placebo. Through 12 months, romosozumab reduced fracture risk versus placebo for non-vertebral fracture (1.4% versus 3.0%; p = 0.004), clinical fracture (1.4% versus 3.6%; p

BACKGROUND: Prior studies of the pharmacogenomics of osteonecrosis of the jaw (ONJ) have had various methodological limitations, including using candidate gene selection as their sole strategy, a small number of ONJ cases, or a study population based on an oncology setting.OBJECTIVES: The aim of our case-control study was to evaluate previously reported associations between genetic factors and ONJ, which were based on either genome-wide association studies (GWAS) or candidate gene approaches. Furthermore, we aimed to identify genetic risk factors for ONJ by using GWAS to determine single-nucleotide polymorphisms (SNPs) with statistically significant differences in frequency between ONJ patients and osteoporosis controls.METHODS: Patients with medically confirmed ONJ and who were registered in the Scandinavian Cohort of ONJ patients were included. Controls from the general population were matched on age (±5 years), sex, and cumulative antiresorptive drug exposure. The ONJ diagnosis date for cases corresponded to the index date for matched controls. DNA isolation, genotyping, and data analyses were performed by Q2/EA Genomics using standard protocols and best practices. Blood or tissue samples for 55 ONJ cases and 125 controls were collected. Due to the low quality of the tissue samples, final analyses were based on blood samples of 40 ONJ cases and 124 controls.RESULTS: We detected no significant genome-wide associations. Of the 43 SNPs with ONJ association in prior studies, none were replicated in our study.CONCLUSIONS: Even though our study sample is the largest to date, we had limited statistical power for GWAS but adequate power for replication analyses. Our study provides no evidence for any genetic predisposition to ONJ. Future studies could increase their statistical power by combining ONJ GWAS datasets and by performing a meta-analysis or pursuing a sequencing strategy in order to identify rare variants.

Objective To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. Design Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. Data sources Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. Eligibility criteria for selecting studies Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. Results The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were more effective than oral bisphosphonates in preventing vertebral fractures. The effect of all treatments was unaffected by baseline risk indicators, except for antiresorptive treatments that showed a greater reduction of clinical fractures compared with placebo with increasing mean age (number of studies=17; β=0.98, 95% confidence interval 0.96 to 0.99). No harm outcomes were seen. The certainty in the effect estimates was moderate to low for all individual outcomes, mainly because of limitations in reporting, nominally indicating a serious risk of bias and imprecision. Conclusions The evidence indicated a benefit of a range of treatments for osteoporosis in postmenopausal women for clinical and vertebral fractures. Bone anabolic treatments were more effective than bisphosphonates in the prevention of clinical and vertebral fractures, irrespective of baseline risk indicators. Hence this analysis provided no clinical evidence for restricting the use of anabolic treatment to patients with a very high risk of fractures. Systematic review registration PROSPERO CRD42019128391.

Pycnodysostosis (MIM #265800) is a subtype of osteopetrosis and is a rare skeletal dysplasia characterized by generalized progressing osteosclerosis. The prevalence is 1–5/1.000.000. Pycnodysostosis is caused by homozygosity or compound heterozygosity for biallelic pathogenic mutations in the cathepsin K gene (CTSK). Insufficient activity of cathepsin K within osteoclasts leads to incomplete bone resorption. Heterozygotic carriers of the mutations have reduced levels of cathepsin K but a normal phenotype. Pycnodysostosis is a systemic skeletal disorder presenting with short stature, facial dysmorphology, maxillary and mandibular hypoplasia, stridor, laryngomalacia and sleep apnea. In addition, osteolysis of the acromial end of the clavicles and brachydactyly are common. There is a generalized, progressive osteosclerosis of the skeleton associated with bone fragility, most frequently affecting the lower extremities. Intraorally, the patients often have a grooved and narrow palate nearly always crowded and misaligned teeth. Isolated growth hormone deficiency or pituitary hypoplasia is found in some patients, but the outcome of growth hormone therapy is variable. Patients with pycnodysostosis have a normal life expectancy. However, craniosynostosis, low energy fractures, chronic pain, respiratory problems and sleep apnea, and dental complications may cause significant morbidity and reduce quality of life. We recommend that patients with pycnodysostosis receive care in a multidisciplinary setting providing access to experienced pediatric or adult endocrinologists, orthopedic surgeons, dentists, craniofacial surgeons, specialists in respiratory medicine, neurology, ophthalmology, and audiology, and physio- and occupational therapists familiar with skeletal dysplasias including osteopetroses.

ObjectiveTo compare in images, obtained by high-resolution peripheral quantitative computed tomography (HR-pQCT) and conventional radiography (CR) of the second and third metacarpophalangeal (MCP) joints, the minimal erosive cortical break needed to differentiate between pathological and physiological cortical breaks.MethodsIn this single-center cross-sectional study, patients with established rheumatoid arthritis (disease duration ≥ 5 yrs) had their second and third MCP joints of the dominant hand investigated by HR-pQCT and CR. Empirical estimation was used to find the optimal cut-off value for the number of erosions and total erosive volume, which were detectable between patients with and without erosions in the second and third MCP joints according to CR.ResultsThe total erosive volume in the second and third MCP joints by HR-pQCT for CR-detected erosive disease was estimated to be 56.4 mm3(95% CI 3.5-109.3). The sensitivity and specificity at this cutpoint were 78% and 83%, respectively, with an area under the receiver-operating characteristic curve (AUC) of 0.81. The optimal cut-off value for the number of erosions by HR-pQCT was 8.5 (95% CI 5.9-11.1) for CR-detected erosive disease in the second and third MCP joints. The sensitivity and specificity at this cutpoint were 74% and 88%, respectively, with an AUC of 0.81.ConclusionErosions by HR-pQCT were larger in patients with erosive damage in the second and third MCP joints by CR. We found that CR had poor sensitivity for detecting erosive disease when the erosive volume was < 56.4 mm3or the number of erosions was < 8.5.

Denosumab, a human monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), is a potent inhibitor of osteoclast differentiation and activity. As the first biologic drug used to treat osteoporosis, denosumab has shown potent anti-resorptive properties and anti-fracture efficacy. The effects of this drug are also unique compared with the effects of bisphosphonates: namely, long-term treatment with this drug results in a continuous gain of bone mineral density, whereas withdrawal of the drug results in a transient overshoot in bone turnover and rapid bone loss. Although the mechanisms for these specific effects remain incompletely understood, emerging experimental and clinical data have started to highlight potential biological and pharmacological mechanisms by which denosumab might affect osteoclasts, as well as osteoblasts, and cause both sustained bone gain and bone loss upon treatment cessation. This Perspective discusses those potential mechanisms and the future studies and clinical implications that might ensue from these findings.

PURPOSE: Cementless tibial components migrate initially until osseointegration and preserve periprosthetic bone. Cemented tibial components are fixed from surgery but loose periprosthetic bone. Little is known about bone formation and resorption biomarkers in relation to component fixation and bone mineral density (BMD) changes of cementless and cemented total knee arthroplasty. We hypothesize a similar migration of cemented and cementless tibial components between 1- and 2-year follow-up indicating a stable long-term fixation.METHODS: In a prospective patient-blinded randomized study, we compared cementless (n = 27) and cemented (n = 26) tibial components with radiostereometry measured migration (MTPM = Maximum Total Point Motion: point of component that migrates the most) and changes in BMD and biochemical bone turnover markers (BTMs) until 24 months after surgery.RESULTS: The mean MTPM between 12 and 24 months were similar between groups with - 0.06 mm (95% CI - 0.23; 0.11) in the cementless group compared to 0.02 mm (95% CI - 0.07; 0.11) in the cemented group. However, there was a higher proportion of cementless components (16/25) than cemented components (7/24) with continuous migration (MTPM > 0.2 mm) (p = 0.02). In the medial and anterior region below the tibial components, the BMD increased by mean 1.8% and 7.4% for cementless components and decreased by mean 8.6% and 4.2% for cemented components until 24-month follow-up. In both groups, BTMs initially showed increased bone resorption (CTx) and bone formation (P1NP) followed by normalization to pre-operative levels at 6 months post-surgery.CONCLUSION: More cementless components than cemented components showed continues migration which suggest a higher risk of early revision. Bone turnover increased post-surgery in both groups, but did not explain the difference in change in periprosthetic BMD.LEVEL OF EVIDENCE: I.

Jakob Bie Granild-Jensen,1,2 Alma Becic Pedersen,2,3 Eskild Bendix Kristiansen,3 Bente Langdahl,2,4 Bjarne Møller-Madsen,2,5 Charlotte Søndergaard,6 Stense Farholt,7 Esben Thyssen Vestergaard,1,2 Gija Rackauskaite8 1Department of Child and Youth, Randers Regional Hospital, Randers, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 5Department of Children’s Orthopedics, Aarhus University Hospital, Aarhus, Denmark; 6Department of Pediatrics and Adolescent Medicine, Gødstrup Regional Hospital, Gødstrup, Denmark; 7Centre for Rare Diseases - Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark; 8Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, DenmarkCorrespondence: Jakob Bie Granild-Jensen, Department of Child and Youth, Randers Regional Hospital, Oestervangsvej 54, Randers, NE, 8930, Denmark, Email jakobgranild@dadlnet.dkBackground: In children with cerebral palsy (CP), fracture rates have been reported to be higher than in the general population but age-specific fracture rates have not been directly compared and the effect of comorbid epilepsy needs elucidation. This impairs decision-making regarding bone health interventions.Aim: We aimed to establish the age-specific fracture rates in children with CP with and without epilepsy in Denmark.Materials and Methods: Data from Danish registers were combined to establish cohorts of children with and without CP born in Denmark from 1997 to 2007. Fracture rates were calculated for 1997– 2016.Results: We identified 1,451 children with CP and 787,159 without CP. Female/male fracture rates per 1,000 person-years were 23/27 with CP and 23/29 without CP. Male sex, epilepsy and anti-seizure medication, but not the diagnosis of CP or GMFCS-level, were associated with higher fracture rates. Relatively more lower extremity fractures occurred in non-ambulant children with CP.Interpretation/Conclusion: We found no increased fracture rates in children with CP when compared to peers; however, fracture locations suggested bone fragility in non-ambulant children. All children with epilepsy and on anti-seizure medication had increased fracture rates. We suggest bone health optimization in these groups.Keywords: fracture rate, cerebral palsy, children, Gross Motor Classification System, epilepsy, anti-seizure medication

Background: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p

Background: The increased fracture risk in persons with diabetes is underestimated by conventional fracture predictors. The aims of this study were to conduct a systematic review and a meta-analysis to compare the levels of bone turnover markers (BTM) in persons with diabetes with and without fractures. Methods: We conducted a systematic literature search. Eligibility criteria were studies investigating BTMs in persons with diabetes with/without fractures. For the meta-analysis, we used the standardised mean difference (SMD) of the markers investigated. Results: We included eight observational studies. Levels of osteocalcin, procollagen type 1 amino terminal propeptide (P1NP), and Insulin-like growth factor-1 (IGF-1) were significantly lower in persons with fracture than in persons without fracture (-0.36 (-0.46, -0.26)) (SMD (95% confidence interval), (-0.57 (-0.75, -0.40)), and (-0.50 (-0.61, -0.39)) respectively. Levels of N-terminal cross-linked telopeptide of type 1 collagen (NTX), sclerostin, and bone-specific alkaline phosphatase (BAP) were significantly higher in persons with fracture (0.24 (0.13, 0.35), (0.47 (0.29, 0.65)), and (0.14 (0.01, 0.27)), respectively, whereas C-terminal cross-linked telopeptide (CTX) showed no difference between the groups. In sensitivity analysis removing one larger study, results were insignificant for osteocalcin, P1NP, NTX, and sclerostin. Conclusions: The results suggest that BTMs may be associated with fracture status in persons with diabetes. Persons with diabetes and fracture have lower levels of formative BTMs and IGF-1, and higher levels of NTX, sclerostin, and BAP compared with no fracture, however, some results were dependent on one larger study.

Osteoporosis is a metabolic bone disorder that is characterized by low bone mass and micro-architectural deterioration of bone tissue. Fractures of the proximal femur, the vertebrae and the distal radius are the most frequent osteoporotic fractures, although most fractures in the elderly are probably at least partly related to bone fragility. The incidence of fractures varies greatly by country, but on average up to 50% of women50 years of age are at risk of fractures. Fractures severely affect the quality of life of an individual and are becoming a major public health problem owing to the ageing population. Postmenopausal osteoporosis, resulting from oestrogen deficiency, is the most common type of osteoporosis. Oestrogen deficiency results in an increase in bone turnover owing to effects on all types of bone cells. The imbalance in bone formation and resorption has effects on trabecular bone (loss of connectivity) and cortical bone (cortical thinning and porosity). Osteoporosis is diagnosed using bone density measurements of the lumbar spine and proximal femur. Preventive strategies to improve bone health include diet, exercise and abstaining from smoking. Fractures may be prevented by reducing falls in high-risk populations. Several drugs are licensed to reduce fracture risk by slowing down bone resorption (such as bisphosphonates and denosumab) or by stimulating bone formation (such as teriparatide). Improved understanding of the cellular basis for osteoporosis has resulted in new drugs targeted to key pathways, which are under development.

Osteogenesis imperfecta (OI) is a hereditary, clinically heterogeneous, connective tissue disorder. The population prevalence of OI in Denmark is 10.6 in 100,000. A hallmark of the disease is frequent fractures that are often precipitated by minimal trauma. The aim of the current study was to compare the fracture rates across the lifespan of patients with OI with that of a reference population from the general population. The present study was a Danish nationwide, population-based, cohort study using register data. We identified 644 (55.6% females) patients in the OI cohort through the Danish National Patient Register and 3361 (55.2% females) persons, randomly selected from the Civil Registry System. A total of 416 patients with OI experienced a total of 1566 fractures during the observation period of median 17.9 years (interquartile range [IQR], 12.4 to 18.0 years), summing to 10137 person years. In comparison, 709 persons in the reference population experienced a total of 1018 fractures during follow-up. Both male and female patients with OI had an increased fracture rate throughout their life. The fracture rate ratio for participants aged 0 to 19 years was 10.7, for participants aged 20 to 54 years 17.2, and for participants aged 55 years and over 4.1 when compared to the reference population. The highest fracture rate was seen in males with OI aged 0 to 19 years (257 fractures per 1000 person-years). The fractures appear to follow the same pattern as in the general population, with a peak during the toddler and adolescent years (incidence rate [IR] 233.9 per 1000 person years), fewer fractures during adulthood (IR 84.5 per 1000 person years), and increased fracture rates in older women (IR 111.9 per 1000 person years). This is the largest register-based nationwide study on the fracture epidemiology of patients with OI. The risk of fractures seems largest in the childhood and adolescent years, and the relative risk of fracture declines with age in patients with OI compared to the general population. © 2016 American Society for Bone and Mineral Research.

ObjectiveVisceral adipose tissue (VAT) is associated with an increased risk of metabolic syndrome (MetS). Recent studies have suggested that VAT negatively affects bone. However, MetS has also been associated with higher estradiol (E2) levels, which is bone protective. We therefore investigated the impact of VAT and E2levels on bone density, structural parameters, and strength estimates.DesignA cross-sectional study was conducted in 72 obese men with MetS to investigate the impact of VAT and E2levels on bone.MethodsBone parameters were assessed by dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HRpQCT) at lumbar spine, proximal femur, radius, and tibia. VAT volume was measured by magnetic resonance imaging (MRI) and sexual hormones were measured in blood samples.ResultsMen with high VAT had a lower bone density at the hip (PP=0.008 andP=0.02), compared with men with low VAT, despite a similar body weight and BMI. Generally, E2levels were low (median 43 pmol/l), and men with E2levels below median had reduced bone density at lumbar spine (P=0.04), and impaired structural parameters at radius and tibia, compared with men with E2levels above median. At the hip, VAT volume and E2levels affected bone density independently and additively, and 50% of men with high VAT and low E2levels had osteopenia with significantly lowerT-score at FN (P=0.004).ConclusionsHigh VAT and low E2negatively affect bone in obese men with MetS. VAT and E2affect bone density at the hip independently and additively, revealing an unexpected high prevalence of osteopenia in middle-aged men with MetS.

Osteogenesis imperfecta (OI) is a heterogeneous rare connective tissue disorder commonly caused by mutations in the collagen type I genes. Pharmacological treatment has been most extensively studied in children, and there are only few studies comprising adult OI patients.i) To review the literature on the current medical management of OI in children and adults, and thereby identify unmet medical needs and ii) to present an overview of possible future treatment options.Individualization and optimization of OI treatment in adults remain a challenge, because available treatments do not target the underlying collagen defect, and available literature gives weak support for treatment decisions for adult patients.Bisphosphonates are still the most widely used pharmacological treatment for adult OI, but the current evidence supporting this is sparse and investigations on indications for choice and duration of treatment are needed.

Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure.BackgroundMetabolic bone disease might commence early in the course of renal failure. This study therefore examined the frequency and severity of the skeletal changes in predialysis chronic renal failure by measurements of bone mineral density (BMD), biochemical markers of bone turnover (osteocalcin, bone-specific alkaline phosphatase, carboxy terminal propeptide of type I collagen, and carboxy-terminal telopeptide of type I collagen), parathyroid hormone (PTH), ionized calcium (Ca++), phosphate (P), and vitamin D metabolites.MethodsThe study was performed in 113 patients (male/female: 82/31) with chronic renal diseases [mean glomerular filtration rate (GFR) of 37 ml/min] and in 89 matched, normal control subjects.ResultsThe patients had significantly (P < 0.05) reduced BMD in the spine (-6.3%), the femur (-12.1%), the forearm (-5.7%), and the total body (-4.2%) as compared with the control subjects. Dividing the patients into quartiles according to GFR revealed that BMD decreased with the gradual decline in renal function at all the measured skeletal sites, but was most pronounced in the femur: 0.63 ± 0.03, 0.74 ± 0.02, 0.77 ± 0.02, and 0.82 ± 0.03 g/cm2 in each quartile from lowest to highest GFR compared with 0.82 ± 0.02 g/cm2 in the control group (P < 0.0001). All of the measured bone markers showed increasing plasma levels with the more advanced stages of renal failure. Serum PTH and serum P levels increased, whereas serum Ca++ and 1,25-dihydroxyvitamin D decreased. BMD Z-scores of the femur and of the forearm correlated to the biochemical markers and to PTH (P < 0.05 to P < 0.0001). The biochemical markers all showed strong correlations to PTH, also when corrected for the effect of the decline in GFR (r = 0.40 to 0.92, P < 0.01 to P < 0.0001).ConclusionSkeletal changes are initiated at an early stage of chronic renal failure, as estimated from reduced BMD and elevated levels of PTH and from the biochemical markers of both bone formation and bone resorption.

The lifetime risk of fracture in white women is 20% for the spine, 15% for the wrist, and 18% for the hip, with an exponential increase in risk beyond the age of 50 years.We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of bisphosphonates to prevent fractures in postmenopausal women? What are the effects of pharmacological treatments other than bisphosphonates to prevent fractures in postmenopausal women? What are the effects of non-pharmacological treatments to prevent fractures in postmenopausal women? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.In this systematic review we present information relating to the effectiveness and safety of the following interventions: alendronate, calcitonin, calcium, calcium plus vitamin D, clodronate, denosumab, etidronate, exercise, hip protectors, hormone replacement therapy, ibandronate, multifactorial non-pharmacological interventions, pamidronate, parathyroid hormone, raloxifene, risedronate, strontium ranelate, vitamin D, vitamin D analogues, and zoledronate.

Serum N-terminal-pro-B-type natriuretic peptide (NT-proBNP) is elevated in systolic heart failure due to volume expansion and pressure overload. Recent data suggest a direct stimulatory effect of thyroid hormones on NT-proBNP synthesis. We examined the influence of acutely induced hyperthyroidism on serum levels of NT-proBNP.Forty-three healthy women were evaluated before and after treatment with 60 mug triiodothyronine (T(3)) daily for 7 days in a noncontrolled study.Before treatment, NT-proBNP was independently and inversely associated with thyrotropin (TSH), (r = -0.34, p = 0.02). T(3) therapy induced an increase in free T(3) (3.3 times, p0.0001) and suppression of TSH ( p0.0001). Heart rate increased by 14% ( p0.0001); weight decreased 0.6 kg ( p0.0001). Median NT-proBNP increased from 53 to 66 pg/mL ( p0.0001). The increase in NT-proBNP levels was independently associated with increase in free T(3) ( p = 0.05) and with reduction in TSH ( p = 0.04), without any association to the changes in cardiac workload.NT-proBNP is influenced by thyroid function among healthy women, as demonstrated by an inverse association between TSH and NT-proBNP. Induction of an acute hyperthyroid state resulted in an increase in NT-proBNP, which seems to reflect a direct action of T(3) on the NT-proBNP secretion rather than an effect of increased cardiac workload.