Treatment of osteoporotic fractures in alkaptonuria by teriparatide stimulates bone formation and decreases fracture rate - A report of two cases.
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ABSTRACT:
SUBMITTER: Ranganath LR
PROVIDER: S-EPMC8649650 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community-dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003-2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003-2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow-up, 20.0% of men had an incident clinical fracture. In multivariate-adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate-adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (-1.8% more annualized loss than in men with ACR <30 mg/g; p < 0.001), but the limited prevalence of macroalbuminuria precluded reliable estimates of its fracture associations. In these community-dwelling older men, we found no association between urine albumin levels and risk of incident clinical fracture, but found a borderline significant, positive association with rate of hip bone loss. © 2016 American Society for Bone and Mineral Research.
| S-EPMC5413394 | biostudies-literature
Project description:Candidate osteoporosis gene variants were examined for associations with fracture risk and bone mineral density (BMD). A total of 9,704 white women were recruited at four U.S. clinical centers and enrolled into the Study of Osteoporotic Fractures, a longitudinal cohort study. Genotyping of 31 polymorphisms from 18 candidate osteoporosis genes was performed in 6,752 women. Incident radiographic fractures were identified at the third and eighth examinations compared with the baseline examination. BMD was measured at the total hip by dual-energy X-ray absorptiometry. Analyses were adjusted for age, clinic site, and self-reported ethnicity. During a mean follow-up of 14.5 years, a total of 849 hip, 658 vertebral, and 2,496 nonhip/nonvertebral fractures occurred in 6,752 women. Women carrying the ALOX15_G48924T T/T genotype had a higher rate of hip fracture (hazard ratio [HR] = 1.33;95% confidence interval [95% CI] = 1.00-1.77) compared with the G/G genotype. Compared with those carrying the PRL_T228C T/T genotype, women with either the C/C (HR = 0.80; 95% CI = 0.67-0.95) or C/T (HR = 0.81; 95% CI = 0.68-0.97) genotype had a lower rate of nonvertebral/nonhip fractures. Women carrying the BMP2_A125611G G/G genotype had a higher rate of vertebral fracture (odds ratio [OR] = 1.51; 95% CI = 1.03-2.23) compared with the A/A genotype. Women with the ESR1_C1335G G/G genotype had a higher rate of vertebral fracture (OR = 1.64; 95% CI = 1.07-2.50) compared with the C/C genotype. Compared with those with the MMP2_C595T C/C genotype, women with the C/T (OR = 0.79; 95% CI = 0.65-0.96) or T/T (OR = 0.44; 95% CI = 0.27-0.72) genotype had a lower rate of vertebral fracture. In conclusion, polymorphisms in several candidate genes were associated with hip, vertebral, and nonhip/nonvertebral fractures but not with total hip BMD in this large population based cohort study.
| S-EPMC2699257 | biostudies-literature
Project description:Genome-wide comparative gene expression analysis of callus tissue of osteoporotic mice (Col1a1-Krm2 and Lrp5-/-) and wild-type were performed to identify candidate genes that might be responsible for the impaired fracture healing observed in Col1a1-Krm2 and Lrp5-/- mice. To investigate bone healing in osteoporosis, we performed fracture healing studies in wild-type mice (C57BL/6 genetic background) and the low bone mass strains Col1a1-Krm2 and Lrp5-/- (Schulze et al., 2010; Kato et al., 2002). Osteotomy was set in femora of female mice and stabilized by a semi-rigid fixator to allow fast bone healing (RM-CM-6ntgen et al., 2010). 21 days post surgery we analyzed the fracture calli by biochemical/histological methods, as well as micro-computed tomography, and observed impaired fracture healing in Col1a1-Krm2 and Lrp5-/- mice in comparison to wild-type. To identify genes that may be responsible for the impaired healing in osteoporotic mice, we performed microarray analysis of three independent callus samples of each genotype. The callus tissue was taken 10 days after surgery, because extensive bone formation took place at this point.
2013-10-25 | E-GEOD-51686 | biostudies-arrayexpress
Project description:PurposeIn osteoporosis, prior fracture is a strong predictor of subsequent fracture. This study aimed to assess the imminent risk of subsequent fracture following an initial fracture in osteoporosis patients in Germany, and to identify clinical and demographic characteristics that are independently associated with subsequent fracture risk.MethodsIn this retrospective, observational cohort study using German real-world claims data, male and female patients aged ≥ 50 years with osteoporosis who experienced an initial ("index") hip/femur, vertebral, forearm/wrist/hand or shoulder/upper arm fracture between 2010 and 2014 were included. The incidence and timing of subsequent fractures during a 1-year follow-up period were analyzed. Independent risk factors for subsequent fracture were identified by multivariate regression analysis.ResultsA total of 18,354 patients (mean age: 77 years; standard deviation: 9.8) were included. Of these, 2918 (15.9%) suffered a subsequent fracture during the 1-year follow-up period. The incidence of subsequent fracture was higher following an index vertebral fracture (18.0%) than after an index forearm/wrist/hand fracture (14.1%) or index hip/femur fracture (12.1%). Subsequent 1-year fracture incidence was generally higher in older patients. Index fracture type, age, epilepsy/use of antiepileptics, and heart failure were all independently associated with subsequent fracture risk.ConclusionOsteoporosis patients in Germany are at imminent risk of subsequent fracture during the first year following an initial fracture. They should be targeted for immediate post-fracture treatment to reduce the risk of further fractures, especially in the presence of specific risk factors such as old age or index vertebral fracture.
| S-EPMC8325652 | biostudies-literature
Project description:IntroductionBoth animal studies and clinical trials have shown that daily parathyroid hormone administration promotes bone fracture healing. We previously found that weekly injections of the recombinant human parathyroid hormone teriparatide at a dosage of 20 μg/kg promoted tibial fracture healing to the same extent as daily injections of teriparatide at a dosage of 10 μg/kg in a rodent model. However, the effect of weekly teriparatide administration on human fracture healing is unreported. This protocol describes a randomised controlled clinical trial designed to evaluate whether weekly administration of teriparatide accelerates fracture repair in humans.Methods and analysisThis single-centre, double-blind, randomised controlled trial will be conducted in Peking University Third Hospital. Eligible patients with Colles' fracture incurred within 48 hours will be randomly divided into two groups (n=40 per group) that will receive 14 weekly subcutaneous injections of either saline or teriparatide (40 μg/week). The primary outcome will be the time taken to achieve radiographic healing, as assessed using the modified radiographic union scale for tibial fractures. The secondary outcomes will be functional assessments, including the self-administered Patient-Rated Wrist Evaluation questionnaire, grip strength and rate of fracture non-union.Ethics and disseminationEthical approval has been obtained from the Peking University Third Hospital Medical Science Research Ethics Committee (M2020207). The findings will be disseminated in peer-reviewed publications.Trial registration numberNCT04473989: protocol version: 1.
| S-EPMC8021745 | biostudies-literature
Project description:We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ?2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2 × 10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3 × 10(-12), and -0.16 SD per G allele, P = 1.2 × 10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3 × 10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9 × 10(-6) and rs2707466: OR = 1.22, P = 7.2 × 10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5 × 10(-13)<P<5.9 × 10(-4)) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture.
| S-EPMC3390364 | biostudies-literature
Project description:Osteoporosis is a highly prevalent bone disease affecting more than 37.5 million individuals in the European Union (EU) and the United States of America (USA). It is characterized by low bone mineral density (BMD), impaired bone quality, and loss of structural and biomechanical properties, resulting in reduced bone strength. An increase in morbidity and mortality is seen in patients with osteoporosis, caused by the approximately 3.5 million new osteoporotic fractures occurring every year in the EU. Currently, different medications are available for the treatment of osteoporosis, including anti-resorptive and osteoanabolic medications. Bisphosphonates, which belong to the anti-resorptive medications, are the standard treatment for osteoporosis based on their positive effects on bone, long-term experience, and low costs. However, not only medications used for the treatment of osteoporosis can affect bone: several other medications are suggested to have an effect on bone as well, especially on fracture risk and BMD. Knowledge about the positive and negative effects of different medications on both fracture risk and BMD is important, as it can contribute to an improvement in osteoporosis prevention and treatment in general, and, even more importantly, to the individual's health. In this review, we therefore discuss the effects of both osteoporotic and non-osteoporotic medications on fracture risk and BMD. In addition, we discuss the underlying mechanisms of action.
| S-EPMC8578161 | biostudies-literature
Project description:Genome-wide comparative gene expression analysis of callus tissue of osteoporotic mice (Col1a1-Krm2 and Lrp5-/-) and wild-type were performed to identify candidate genes that might be responsible for the impaired fracture healing observed in Col1a1-Krm2 and Lrp5-/- mice.
2013-10-25 | GSE51686 | GEO
Project description:ObjectiveTeriparatide has been increasingly utilized in the management of osteoporosis. The efficacy of low and high dose teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain is unknown. We sought to determine the efficacy of teriparatide on these patient-important outcomes using a systematic review and meta-analysis.MethodsA systematic search of electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL) was performed to identify randomized controlled trials (RCTs) that evaluate teriparatide to any comparator for the treatment of osteoporosis in postmenopausal women. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria were used by two independent reviewers to assess the strength and quality of evidence.ResultsA total of 20 studies (n = 6024) were included in this review, with 2855 patients receiving teriparatide and 3169 patients receiving placebo or control treatment. A teriparatide dose of 20 μg/day increased lumbar spine bone mineral density (BMD) (standardized mean difference (SMD) 0.34 standard deviation (SD) units higher (95% CI 0.19-0.48 SDs higher) in comparison to placebo. Relative to anti-resorptive agents, 20 μg/day of teriparatide had a range from 0.14 SD units to 0.96 SD units higher (95% CI, 0.08 SDs lower to 0.36 SDs higher, CI, 0.33-1.59 SDs higher, respectively). 20 μg/day teriparatide had a significant effect on pain severity to placebo or control (SMD 0.80, 95% CI, 1.16-0.43 SDs lower) and also decreased the incidence of vertebral fractures compared to placebo (relative risk 0.31, 95% CI 0.21 to 0.46). Arthralgia and extremity pain incidence were also calculated; there were 15 and 8 fewer events per 1000 patients with the use of 20 μg/day of teriparatide compared to placebo or control, respectively.ConclusionHigh quality evidence supports the utilization of teriparatide 20 μg/day dose to significantly improve lumbar spine BMD and decrease incidence of vertebral fractures and pain severity relative to all comparators. 40 μg/day dose of teriparatide demonstrated significantly better results with prolonged treatment. This data is valuable for clinicians involved in the care of this growing demographic of patients. Further investigation on the safety and efficacy of teriparatide in higher doses for the long-term treatment of osteoporosis in postmenopausal women should be conducted through high-quality clinical trials.
| S-EPMC7591342 | biostudies-literature
Project description:Study of Osteoporotic Fractures (SOF)
| PRJNA170110 | ENA