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1.
Semin Reprod Med ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33784746

RESUMO

Accelerated bone loss and muscle loss coexist in women with premature ovarian insufficiency (POI), but there are significant gaps in our understanding of musculoskeletal health in POI. This review describes estrogen signaling in bone and its role in skeletal health and disease. Possible mechanisms contributing to bone loss in different forms of POI and current evidence regarding the utility of available diagnostic tests and therapeutic options are also discussed. A literature review from January 2000 to March 2020 was conducted to identify relevant studies. Women with POI experience significant deterioration in musculoskeletal health due to the loss of protective effects of estrogen. In bone, loss of bone mineral density (BMD) and compromised bone quality result in increased fracture risk; however, tools to assess bone quality such as trabecular bone score (TBS) need to be validated in this population. Timely initiation of HRT is recommended to minimize the deleterious effects of estrogen deficiency on bone in the absence of contraindications; however, the ideal estrogen replacement regimen remains unknown. POI is associated with compromised bone health, regardless of the etiology. Ongoing research is warranted to refine our management strategies to preserve bone health in women with POI.

2.
Contemp Clin Trials ; 104: 106347, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33684596

RESUMO

BACKGROUND: The D-Health Trial aims to determine whether monthly high-dose vitamin D supplementation can reduce the mortality rate and prevent cancer. We did not have adequate statistical power for subgroup analyses, so could not justify the high cost of collecting blood samples at baseline. To enable future exploratory analyses stratified by baseline vitamin D status, we developed models to predict baseline serum 25 hydroxy vitamin D [25(OH)D] concentration. METHODS: We used data and serum 25(OH)D concentrations from participants who gave a blood sample during the trial for compliance monitoring and were randomised to placebo. Data were partitioned into training (80%) and validation (20%) datasets. Deseasonalised serum 25(OH)D concentrations were dichotomised using cut-points of 50, 60 and 75 nmol/L. We fitted boosted regression tree models, based on 13 predictors, and evaluated model performance using the validation data. RESULTS: The training and validation datasets had 1788 (10.5% <50 nmol/L, 23.1% <60 nmol, 48.8 <75 nmol/L) and 447 (11.9% <50 nmol/L, 25.7% <60 nmol/L, and 49.2% <75 nmol/L) samples, respectively. Ambient UV radiation and total intake of vitamin D were the strongest predictors of 'low' serum 25(OH)D concentration. The area under the receiver operating characteristic curves were 0.71, 0.70, and 0.66 for cut-points of <50, <60 and <75 nmol/L respectively. CONCLUSIONS: We exploited compliance monitoring data to develop models to predict serum 25(OH)D concentration for D-Health participants at baseline. This approach may prove useful in other trial settings where there is an obstacle to exhaustive data collection.

3.
Curr Osteoporos Rep ; 19(2): 123-130, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33587247

RESUMO

PURPOSE OF REVIEW: Atypical femur fractures (AFFs) are rare subtrochanteric or diaphyseal fractures regarded as side effects of bisphosphonates (BPs), possibly with a genetic background. Here, we summarize the most recent knowledge about genetics of AFFs. RECENT FINDINGS: AFF has been reported in 57 patients with seven different monogenic bone disorders including hypophosphatasia and osteogenesis imperfecta; 56.1% had never used BPs, while 17.5% were diagnosed with the disorder only after the AFF. Gene mutation finding in familial and sporadic cases identified possible AFF-related variants in the GGPS1 and ATRAID genes respectively. Functional follow-up studies of mutant proteins showed possible roles in AFF. A recent small genome-wide association study on 51 AFF cases did not identify significant hits associated with AFF. Recent findings have strengthened the hypothesis that AFFs have underlying genetic components but more studies are needed in AFF families and larger cohorts of sporadic cases to confirm previous results and/or find novel gene variants involved in the pathogenesis of AFFs.

4.
J Diabetes Investig ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33605046

RESUMO

INTRODUCTION: Diabetes and bone health are closely related. We examined the incidence and risk factors of hip fractures in Chinese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this prospective cohort, we consecutively enrolled 22,325 adults with T2D above the age of 40 years in the Hong Kong Diabetes Register between 1994 and 2015 with crude hip fracture incidence rate censored in 2017. RESULTS: At baseline, the mean age of this cohort was 60.9 ± 10.5 years (mean duration of diabetes 6 years, 52.4% male). During a mean ± standard deviation (SD) follow-up period of 8.7 ± 5.2 years with 193,553 person-years, 603 patients were hospitalized due to hip fractures with an incidence (95% confidence interval, CI) of 315.1 (290.4-341.3) per 100,000 person-years. On multivariable analysis with competing death risk adjusted, the independent hazard ratios (95% CI) for hip fractures in T2D were 2.01 (1.61-2.51) for female sex, 1.08 (1.07-1.09) for age, 0.93 (0.90-0.95) for body mass index, 1.52 (1.25-1.85) for albuminuria and 1.12 (1.02-1.23) for low density lipoprotein-cholesterol. In men, the 30-day, 1-year and 5-year post-hip fracture mortality rate (95% CI) were 5.8 (2.4-9.1) %, 29.2 (22.3-35.5) % and 65.9 (57.3-72.8) % respectively. The corresponding rates in women were 3.4 (1.6-5.1) %, 18.6 (14.7-22.4) %, and 46.8 (40.9-52.1) %. CONCLUSIONS: Southern Chinese patients with T2D have a high risk of hip fracture associated with suboptimal cardiometabolic-renal risk factors and a high post-fracture mortality rate. The effects of improving modifiable risk factors on bone health warrants further evaluation.

5.
Semin Reprod Med ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33418593

RESUMO

Accelerated bone loss and muscle decline coexist in women with premature ovarian insufficiency (POI), but there are significant gaps in our understanding of musculoskeletal health in POI. This article is the first of a two-part review which describes estrogen signaling in muscle and its role in musculoskeletal health and disease. Current evidence regarding the utility of available diagnostic tests and therapeutic options is also discussed. A literature review from January 2000 to March 2020 was conducted to identify relevant studies. Women with POI experience significant deterioration in musculoskeletal health due to the loss of protective effects of estrogen. In addition to bone loss, muscle decay and dysfunction is now increasingly recognized. Nevertheless, there is a paucity of validated tools to assess muscle parameters. There is a growing need to acknowledge bone-muscle codependence to design new therapies which target both muscle and bone, resulting in improved physical performance and reduced morbidity and mortality. More high-quality research and international collaborations are needed to address the deficiencies in our understanding and management of musculoskeletal health in women with POI.

7.
Obes Rev ; 22(5): e13187, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33491333

RESUMO

Sarcopenia and obesity are common conditions in older adults that may have differing effects on falls and fracture risk. This systematic review and meta-analysis aimed to determine whether older adults with sarcopenic obesity have increased risk of falls and fractures or lower bone mass compared with older adults with sarcopenia, obesity, or neither condition. Twenty-six studies (n = 37,124) were included in the systematic review and 17 (n = 31,540) were included in the meta-analysis. Older adults with sarcopenic obesity had lower femoral neck areal bone mineral density (aBMD) compared with those with obesity alone but had higher femoral neck aBMD compared with counterparts with sarcopenia alone (both P < 0.05). Older adults with sarcopenic obesity had higher nonvertebral fracture rates (incidence rate ratio: 1.88; 95% confidence intervals: 1.09, 3.23; based on two studies), compared with those with sarcopenia alone, and also had higher falls risk compared with controls (risk ratio: 1.30; 95% confidence intervals: 1.10, 1.54) and obesity alone (risk ratio: 1.17; 95% confidence intervals: 1.01, 1.36). In conclusion, this systematic review and meta-analysis has demonstrated that older adults with sarcopenic obesity are at increased risk of adverse musculoskeletal outcomes compared with individuals with obesity, sarcopenia, or neither condition. These data support the need for developing interventions to improve bone health and physical function in this population.

8.
Lancet Diabetes Endocrinol ; 9(2): 69-81, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33444565

RESUMO

BACKGROUND: Observational studies have linked vitamin D deficiency with acute respiratory tract infection, but results from randomised controlled trials are heterogeneous. We analysed data from the D-Health Trial to determine whether supplementing older Australian adults, recruited from the general population, with monthly doses of vitamin D reduced the risk, duration, and severity of acute respiratory tract infections. METHODS: We used data from the D-Health Trial, a randomised, double-blind, placebo-controlled trial of monthly vitamin D supplementation, for which acute respiratory infection was a pre-specified trial outcome. Participants were supplemented and followed for up to 5 years. The trial was set within the Australian general population, using the Commonwealth Electoral Roll as the sampling frame, but also allowing some volunteers to participate. Participants were men and women aged 60 to 79 years (with volunteers up to age 84 years). Participants were randomly assigned to receive either vitamin D or placebo (1:1) using computer-generated permuted block randomisation, which was stratified by age, sex, and state. This was an automated process and the assignment list was not visible to study staff or investigators. Active and placebo gel capsules, identical in appearance to ensure masking, were labelled A and B and the code was not available to study staff or investigators. Participants were asked to report occurrence of acute respiratory symptoms over the previous month via annual surveys, and a subset of participants completed 8-week respiratory symptom diaries in winter. As part of our process to maintain blinding, a random sample of participants was selected for analysis of survey data and a separate sample selected for analysis of diary data. Blood samples were obtained from a random sample of participants (about 450 per group per year) and serum 25-hydroxy vitamin D (25[OH]D) concentrations were measured to monitor adherence. We used regression models to estimate odds ratios (OR), rate ratios, and rate differences. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763. FINDINGS: Between Jan 13, 2014, and May 26, 2015, 421 207 invitations were sent, 40 824 people were interested in participating, and 21 315 participants were recruited and randomised. Of the 16 000 participants selected for potential analysis of survey data, 15 373 were included in the analysis; 295 in the vitamin D group and 332 in the placebo group who were missing data for all five annual surveys were excluded from the analysis. Of the 3800 selected for potential analysis of diary data, 3070 were invited to complete the diaries because 730 had already withdrawn. 2598 people were included in the analysis; 218 people in the vitamin D group and 254 in the placebo group were missing data and were therefore excluded from the analysis. In blood samples collected from randomly sampled participants throughout the trial, the mean serum 25(OH)D concentration was 114·8 (SD 30·3) nmol/L in the vitamin D group and 77·5 (25·2) nmol/L in the placebo group. Vitamin D supplementation did not reduce the risk of acute respiratory tract infection (survey OR 0·98, 95% CI 0·93 to 1·02; diary OR 0·98, 0·83 to 1·15). Analyses of diary data showed reductions in the overall duration of symptoms and of severe symptoms, but these were small and unlikely to be clinically significant. INTERPRETATION: Monthly bolus doses of 60 000 IU of vitamin D did not reduce the overall risk of acute respiratory tract infection, but could slightly reduce the duration of symptoms in the general population. These findings suggest that routine vitamin D supplementation of a population that is largely vitamin D replete is unlikely to have a clinically relevant effect on acute respiratory tract infection. FUNDING: National Health and Medical Research Council.


Assuntos
Infecções Respiratórias/tratamento farmacológico , Vitamina D/uso terapêutico , Austrália , Ensaios Clínicos como Assunto , Humanos , Infecções Respiratórias/etiologia , Resultado do Tratamento , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico
9.
J Bone Miner Res ; 36(3): 619-620, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33314267
10.
J Clin Oncol ; : JCO2002906, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290127
11.
Artigo em Inglês | MEDLINE | ID: mdl-33211870

RESUMO

CONTEXT: Effects of long-term exposure to denosumab in subjects with renal insufficiency are unknown. OBJECTIVE: This post hoc analysis evaluates the long-term safety and efficacy of denosumab in subjects with mild-to-moderate CKD (stages 2 and 3) using data from the pivotal phase 3, double-blind, 3-year FREEDOM (NCT00089791) and open-label, 7-year extension (NCT00523341) studies. SUBJECTS AND METHODS: Women aged 60-90 years with bone mineral density (BMD) T-score <-2.5 to >-4.0 at the total hip or lumbar spine were randomized 1:1 to denosumab 60 mg SC Q6M (long-term arm) or placebo (cross-over arm) in FREEDOM; eligible subjects could enroll in the extension to receive denosumab 60 mg SC Q6M. Change in estimated glomerular filtration rate (eGFR) from study baseline and annualized rates of fracture and adverse events (AEs) were the main outcome measures. RESULTS: Most subjects (1259/1969 [64%] long-term arm; 1173/1781 [66%] crossover arm) with baseline CKD stage 2 or 3 remained within the same CKD subgroup at study completion; <3% progressed to CKD stage 4. Subjects in all eGFR subgroups showed similar, persistent BMD gains over time and a low incidence of fractures. The percentage of subjects reporting serious AEs was similar among renal subgroups (normal, CKD stage 2, CKD stage 3a, CKD stage 3b) for both the long-term (54% vs 52% vs 57% vs 58%) and crossover (43% vs 42% vs 43% vs 68%) arms, except CKD stage 3b subgroup, crossover arm. CONCLUSION: The safety and efficacy of denosumab did not differ among subjects with mild-to- moderate CKD.

12.
Obesity (Silver Spring) ; 28(11): 2232-2241, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33012137

RESUMO

OBJECTIVE: Obesity is commonly defined by BMI rather than adiposity, which may have differential effects on musculoskeletal health. Musculoskeletal outcomes were compared in older adults with normal adiposity and normal BMI (NA-NBMI), those with high adiposity but normal BMI (HA-NBMI), and those with high adiposity and high BMI (HA-HBMI). METHODS: In 3,411 70-year-olds, obesity was defined as BMI ≥ 30 kg/m2 and adiposity as body fat percentage ≥ 25% (men) or ≥ 35% (women) from dual-energy x-ray absorptiometry. Bone parameters were measured by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography. Sarcopenia was defined as low handgrip strength with or without low appendicular lean mass. Falls were self-reported 6 and 12 months later. RESULTS: Prevalence of NA-NBMI, HA-NBMI, and HA-HBMI was 14.2%, 68.1%, and 17.7%, respectively. Compared with HA-HBMI, HA-NBMI had increased likelihood for sarcopenia (adjusted odds ratio: 3.99; 95% CI: 1.41-11.32) and osteoporosis (2.91; 95% CI: 2.35-3.61) but similar likelihood of falls (P > 0.05). HA-NBMI had lower values for bone geometry parameters, as well as grip strength, than both NA-NBMI and HA-HBMI (all P < 0.05). CONCLUSIONS: High adiposity without high BMI is more common than BMI-defined obesity in older Swedish adults but does not provide similar protection from osteoporosis and sarcopenia.

13.
J Bone Miner Res ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118663

RESUMO

Noncommunicable diseases (NCD) are rapidly rising in Africa, with multimorbidity increasing the burden on health and social care. Osteoporosis and cardiovascular disease (CVD) share common risk factors; both often remain undiagnosed until a major life-threatening event occurs. We investigated the associations between cardiac workload, peripheral vascular calcification (PVC), and bone parameters in Gambian adults. The Gambian Bone and Muscle Aging Study (GamBAS) recruited 249 women and 239 men aged 40 to 75+ years. Body composition and areal bone mineral density (aBMD) were measured using dual-energy X-ray absorptiometry; peripheral quantitative computed tomography (pQCT) scans were performed at the radius and tibia. Supine blood pressure and heart rate were measured and used to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia pQCT scans. Sex interactions were tested (denoted as p-int); adjustments were made for residuals of appendicular lean mass (ALM) and fat mass (FM). There were negative associations between rate pressure product and aBMD in women only, all p-int < .05; after adjustment for ALM residuals, for every 10% increase in rate pressure product, aBMD was lower at the whole body (-0.6% [-1.2, -0.1]), femoral neck (-0.9% [-1.8, -0.05]), L1 to L4 (-0.6% [-1.7, 0.5]), and radius (-1.9% [-2.8, -0.9]); there were similar associations when adjusted for FM residuals. Similar negative associations were found between pulse pressure and aBMD in women only. PVC were found in 26.6% men and 22.5% women; women but not men with calcification had poorer cardiac health and negative associations with aBMD (all sites p-int < .001). There were consistent associations with cardiac parameters and pQCT outcomes at the radius and tibia in women only. Multiple markers of cardiac health are associated with poorer bone health in Gambian women. In the context of epidemiological transition and changing NCD burden, there is a need to identify preventative strategies to slow/prevent the rising burden in CVD and osteoporosis in Sub-Saharan Africa. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

14.
J Bone Miner Res ; 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32780899

RESUMO

The cardiovascular safety of denosumab has not yet been evaluated in a systematic review. This systematic review and meta-analysis sought to quantify the number of randomized controlled trials (RCTs) of denosumab (against comparators) reporting cardiovascular adverse events (CAEs) and examine the balance of CAEs between treatment arms. MEDLINE, Embase, and clinicaltrials.gov were searched from inception to October 26, 2019, for RCTs of denosumab versus comparators for any indication. Included trials were randomized, enrolled ≥100 participants, and reported bone-related outcomes. Primary outcome for analysis was all CAEs, a composite endpoint representing summation of all CAEs as reported by included trials. Secondary outcomes included major adverse cardiovascular events (MACE). Data were pooled using a fixed effects model to determine relative risk (RR) and 95% confidence interval (95% CI). Risk of bias was assessed using the Cochrane risk-of-bias tool. Of 554 records screened, 49 were included, while 36 reported CAEs. Twenty-seven included trials (12 eligible for meta-analysis) were conducted in 13,202 postmenopausal women. Compared with bisphosphonates, there was a 46% (95% CI 1.05 to 2.02) increase in CAEs (85/2136 events in denosumab-treated versus 58/2131 events in bisphosphonate-treated; seven trials). There was a similar imbalance in a five-point (stroke, myocardial infarction, cardiovascular death, heart failure, atrial fibrillation) MACE endpoint (28/2053 versus 12/2050; RR = 2.33 [1.19 to 4.56]). Compared with placebo-treated women, there was no imbalance in total CAEs (439/4725 events in denosumab versus 399/4467 in placebo; RR = 0.79 [0.41 to 1.52]; seven trials). No imbalance in total AEs (versus bisphosphonates: 0.98 [0.92 to 1.04]; versus placebo: 0.99 [0.98 to 1.01]) occurred. Other indications showed no statistically significant results. The excess CAEs in postmenopausal women treated with denosumab compared with bisphosphonates, but not placebo, indirectly supports claims that bisphosphonates may suppress CAEs. Future trials should use standardized CAE reporting to better describe cardiovascular effects of bone active medications. (PROSPERO: CRD42019135414.) © 2020 American Society for Bone and Mineral Research (ASBMR).

15.
Bone ; 140: 115546, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32730938

RESUMO

PURPOSE: The aim of this study was to determine and compare risk factors associated with incident fractures in older adults with and without obesity, defined by both body mass index (BMI) and body fat percentage. METHODS: 1,099 older adults (mean ± standard deviation age = 63.0 ± 7.5) years, participated in this prospective cohort study. Obesity status at baseline was defined by BMI (≥30 kg/m2) obtained by anthropometry and body fat percentage (≥30% for men and ≥40% for women) assessed by dual-energy X-ray absorptiometry (DXA). Total hip and lumbar spine areal bone mineral density (aBMD) were assessed by DXA up to five years. Incident fractures were self-reported up to 10 years. RESULTS: Prevalence of obesity was 28% according to BMI and 43% according to body fat percentage. Obese older adults by BMI, but not body fat percentage, had significantly higher aBMD at the total hip and spine compared with non-obese (both p-value<0.05). Obese older adults by body fat percentage had significantly higher likelihood of all incident fractures (OR: 1.71; CI:1.08, 2.71) and non-vertebral fractures (OR: 1.88; CI:1.16, 3.04) compared with non-obese after adjusting for confounders. Conversely, obese older adults by BMI had a significantly lower likelihood (OR: 0.54; CI:0.31, 0.94) of non-vertebral fractures although this was no longer significant after adjustment for total hip aBMD (all p-value > 0.05). Mediation analysis confirmed that aBMD meditated the effects of BMI, but not body fat percentage, on all incident fractures. Higher baseline falls risk score was the only consistent predictor of increased likelihood of incident fracture in obese individuals only, according to both BMI and body fat percentage (both p-value<0.05). CONCLUSIONS: Obesity defined by body fat percentage is associated with increased likelihood of incident fractures in community-dwelling older adults, whereas those who are obese according to BMI have reduced likelihood of incident fracture which appears to be explained by higher aBMD. Falls risk assessment may improve identification of obese older adults at increased risk of incident fractures.

16.
J Clin Endocrinol Metab ; 105(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32717068

RESUMO

CONTEXT: The cardiovascular (CV) safety of oral bisphosphonates (oBPs) is uncertain. OBJECTIVE: Determine the risk of CV events in oBP users referred for bone mineral density (BMD) testing compared with matched controls. DESIGN: Cohort study. SETTING: Danish national prescription registry enriched with local hospital data from Odense. PARTICIPANTS: Individuals aged ≥45 years referred for BMD testing. EXPOSURE: oBP. OUTCOMES: Hospitalization for any CV event. Secondary study outcomes were specific CV events. Negative (inguinal hernia surgery and ingrown toenail) and positive (fragility fracture) control outcomes assessed systemic bias. Cox proportional hazards models were fitted to estimate hazard ratio (HR) and 95% confidence intervals. RESULTS: There were 2565 oBP users (82.6% women) and 4568 (82.3% women) propensity score-matched controls. Alendronate accounted for 96% of oBP prescription. A total of 406 (15.8%) CV events occurred in oBP users (rate = 73.48 [66.67-80.98]); rate = events divided by person-time; and 837 (18.3%) events in controls (rate = 104.73 [97.87-112.07]) with an adjusted HR of 0.68 (95% CI 0.60-0.77). Additional adjustment for BMD did not attenuate estimates (HR 0.67; 95% CI 0.58-0.78]. Similar results were seen for secondary outcomes where risk reductions were seen regarding atrial fibrillation, stroke, heart failure, and aneurysms. Positive and negative control outcome analyses identified minimal residual confounding. CONCLUSION: Oral BP users experienced a 33% reduced risk of CV events. This observational real-world study adds to a growing body of evidence for cardioprotection by oBP that warrants testing in a randomized setting.

17.
J Clin Oncol ; 38(26): 2971-2980, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32614699

RESUMO

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent but morbid and potentially serious condition associated with antiresorptive and antiangiogenic therapies. Although MRONJ can be prevented by optimizing oral health, management of established cases is supportive and remains challenging. Teriparatide, an osteoanabolic agent that improves bone healing in preclinical studies and in chronic periodontitis, represents a potential treatment option. PATIENTS AND METHODS: In a double-blind, randomized, controlled trial, 34 participants with established MRONJ, with a total of 47 distinct MRONJ lesions, were allocated to either 8 weeks of subcutaneous teriparatide (20 µg/day) or placebo injections, in addition to calcium and vitamin D supplementation and standard clinical care. Participants were observed for 12 months, with primary outcomes that included the clinical and radiologic resolution of MRONJ lesions. Secondary outcomes included osteoblastic responses as measured biochemically and radiologically and changes in quality of life. RESULTS: Teriparatide was associated with a greater rate of resolution of MRONJ lesions (odds ratio [OR], 0.15 v 0.40; P = .013), and 45.4% of lesions resolved by 52 weeks compared with 33.3% in the placebo group. Teriparatide was also associated with reduced bony defects at week 52 (OR, 8.1; P = .017). The incidence of adverse events was balanced between groups, including nausea, anorexia, and musculoskeletal pain, most of mild severity. CONCLUSION: Teriparatide improves the rate of resolution of MRONJ lesions and represents an efficacious and safe treatment for it.

18.
J Bone Miner Res ; 35(7): 1333-1342, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32445228

RESUMO

In the Active-Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) clinical trial (NCT01631214), 1 year of romosozumab followed by alendronate reduced the risk of vertebral and nonvertebral fractures compared to alendronate alone in women with prevalent fracture. We performed post hoc analyses of data from patients in ARCH (romosozumab, n = 1739; alendronate, n = 1726) who had a baseline BMD measurement and received at least one open-label alendronate dose. We evaluated 1-year mean BMD and corresponding T-score changes; proportions of patients achieving T-scores > -2.5 at the total hip (TH), femoral neck (FN), and lumbar spine (LS); and group differences in fracture rates after 12 months, while all participants were on alendronate. Subsequently, we investigated the relationship between T-scores achieved at the TH, FN, and LS at 12 months and subsequent fracture incidence. At 1 year, mean change from baseline in TH BMD was 6.3% (T-score change 0.31) with romosozumab versus 2.9% (T-score change 0.15) with alendronate (p < .001). The proportion of patients with TH T-score > -2.5 increased from 34% at baseline to 55% after 1 year of romosozumab and from 32% at baseline to 44% after 1 year of alendronate. Compared with patients receiving alendronate in year 1, those receiving romosozumab had a 75% reduction in new or worsening vertebral fracture (p < .001) in year 2, and a 19% reduction in nonvertebral fracture (p = .120) and 40% reduction in hip fracture (p = .041) during the open-label period. TH and FN T-scores achieved at month 12 were associated with subsequent nonvertebral and vertebral fracture rates and the relationships were independent of treatment received. LS T-score at 12 months was associated with vertebral but not nonvertebral fracture risk. We conclude that 1 year of romosozumab leads to larger BMD gains versus alendronate, and that the T-score achieved with either therapy is related to subsequent fracture risk. These data support the use of T-score as a therapeutic target for patients with osteoporosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

19.
Arch Osteoporos ; 15(1): 38, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125551

RESUMO

PURPOSE: To determine whether geographic variation exists in osteoporosis knowledge, management, and barriers to care in the setting of premature ovarian insufficiency (POI), among general practitioners (GPs) and women with POI. METHODS: Australian GPs completed an online questionnaire regarding osteoporosis knowledge, barriers to care and educational preferences for managing osteoporosis in POI. Women with POI/early menopause (EM) completed an online questionnaire regarding osteoporosis knowledge, risk factors and health beliefs. Clinicians and consumers in metropolitan areas were compared to those in rural areas. RESULTS: Of 688 GP respondents, 62.2% practised in major capital cities, 13.1% in major regional cities, 7.8% in regional centres, 8.7% in rural areas and 8.1% in remote areas. Mean ± SD osteoporosis knowledge score was 9.1 ± 1.5/13, with no difference by location. Forty-one percent of GPs reported barriers to care which varied by location. Of 316 women with POI/EM, 61.1% lived in metropolitan, 22.5% in regional, 11.7% in rural and 4.4% in remote locations. The mean osteoporosis knowledge score was 8.2 ± 3.1/20, with lower scores in women living in rural and remote versus metropolitan locations (difference - 1.3; 95% CI - 2.3, - 0.25; p = 0.02). Women in rural areas were less likely to use vitamin D supplements and more likely to have a family history of osteoporosis (both p < 0.05). CONCLUSIONS: GP knowledge gaps and specific, location-dependent care barriers for osteoporosis in POI were identified. Geographic differences in osteoporosis knowledge and risk factors exist in women with POI/EM. These factors require consideration when designing programs to improve bone health in POI.


Assuntos
Clínicos Gerais/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Acesso aos Serviços de Saúde/estatística & dados numéricos , Osteoporose/psicologia , Insuficiência Ovariana Primária/psicologia , Adulto , Austrália , Feminino , Geografia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Insuficiência Ovariana Primária/complicações , Fatores de Risco , População Rural/estatística & dados numéricos , Inquéritos e Questionários , População Urbana/estatística & dados numéricos
20.
Bone ; 135: 115319, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32179169

RESUMO

Asian race, younger age, higher body mass index (BMI) and antiresorptive drugs have all been associated with atypical femur fractures (AFFs). This increased risk of AFF in Asians is important as by 2050, >50% of hip fractures globally will occur in Asia, with an increased demand for antiresorptive drugs being likely. It is also currently unclear whether AFF risk is increased in all Asian subgroups. We therefore aimed to identify the incidence of AFFs in an Australian tertiary hospital, the contribution of ethnic origin to AFF risk, and determine other clinical risk factors for AFF. From January 1, 2009 to December 31, 2017, 97 AFFs (82 complete and 15 incomplete) occurred in 71 individuals in the overall study population of 204,358. Patients with AFF were more likely to be female (88.7% vs 69.1%, p < 0.001) and younger [median (IQR): 74(52-92) years vs 83(75-88) years, p < 0.001] than the "typical" femur fracture group (n = 3330). The cumulative incidence rate of AFF was 4.2 per 100,000 person-years, far lower than for any ICD-10 AM coded "typical" femur fracture (202.9 per 100,000 person-years). Asians were 3.4 (95%CI, 2.1-5.6) times more likely to sustain an AFF than non-Asians, the highest incidence being in those from South East Asian countries (16.6 per 100,000 person years), suggesting differences in risk between Asian countries. In the nested case-control study, bisphosphonate use was an independent association with AFF development. We conclude Asian ethnicity is an important association with AFF in this large Australian cohort.

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