Repeating Vertebral Fracture Assessment: 2019 ISCD Official Position.

Vertebral fracture (VF) is the most common type of osteoporotic fracture. VFs are associated with a decline in quality of life and high morbidity and mortality. The presence of a VF is a significant risk factor for developing another fracture; however, most VFs are not clinically recognized and diagnosed. Vertebral fracture assessment by dual-energy X-ray absorptiometry is a low cost, low radiation, convenient, and reliable method to identify VFs. The finding of a previously unrecognized VF may change the assessment of fracture risk, diagnostic classification, and treatment strategies. Vertebral fracture assessment or radiographic lateral spine imaging should be repeated in patients with continued high risk for fracture (e.g., historical height loss >4 cm [>1.5 inches], self-reported but undocumented vertebral fracture, or glucocorticoid therapy equivalent to ≥5 mg of prednisone or equivalent per day for greater than or equal to 3 months).

Obesity, Bariatric Surgery, and Vitamin D.

The high prevalence of obesity is a worldwide problem associated with multiple comorbidities, including cardiovascular diseases. Vitamin D deficiency with secondary hyperparathyroidism is common in obese individuals and can be aggravated after bariatric surgery. Moreover, there is no consensus on the optimal supplementation dose of vitamin D in postbariatric surgical patients. We present new data on the variability of 25(OH)D response to supplementation in postmenopausal obese women. It is important to recognize and treat vitamin D deficiency before bariatric surgery to avoid postoperative complications, such as metabolic bone disease with associated high fracture risk. The objective of this article is to discuss the bone metabolism consequences of vitamin D deficiency after bariatric surgery.

The Clinical Utility of Vertebral Fracture Assessment in Predicting Fractures.

Vertebral fracture (VF) is the most common type of osteoporotic fracture. VFs are associated with diminished quality of life and high morbidity and mortality. The presence of a VF, especially a recent one, is an important risk factor for developing another fracture. However, most VFs are not clinically recognized. VF assessment by dual-energy X-ray absorptiometry is a convenient, low-cost, low-radiation, reliable method to identify VFs during bone mineral density measurement. The finding of a previously unrecognized VF may change the diagnostic classification, assessment of fracture risk, and treatment strategies. This paper focuses on the utility of VF assessment in clinical practice.

Goal-directed osteoporosis treatment: ASBMR/BHOF task force position statement 2024.

The overarching goal of osteoporosis management is to prevent fractures. A goal-directed approach to long-term management of fracture risk helps ensure that the most appropriate initial treatment and treatment sequence is selected for individual patients. Goal-directed treatment decisions require assessment of clinical fracture history, vertebral fracture identification (using vertebral imaging as appropriate), measurement of bone mineral density (BMD), and consideration of other major clinical risk factors. Treatment targets should be tailored to each patient's individual risk profile and based on the specific indication for beginning treatment, including recency, site, number and severity of prior fractures, and BMD levels at the total hip, femoral neck, and lumbar spine. Instead of first-line bisphosphonate treatment for all patients, selection of initial treatment should focus on reducing fracture risk rapidly for patients at very high and imminent risk, such as in those with recent fractures. Initial treatment selection should also consider the probability that a BMD treatment target can be attained within a reasonable period of time and the differential magnitude of fracture risk reduction and BMD impact with osteoanabolic versus antiresorptive therapy. This position statement of the ASBMR/BHOF Task Force on Goal-Directed Osteoporosis Treatment provides an overall summary of the major clinical recommendations about treatment targets and strategies to achieve those targets based on the best evidence available, derived primarily from studies in older postmenopausal women of European ancestry.

Goal-directed treatment can help healthcare providers recommend the best treatments for individual patients to prevent fractures. The goal-directed strategy considers the site, number, and recency of prior fractures. This may require imaging for spine fractures, which may not have caused pain. Treatment decisions also require bone mineral density (BMD) measurement and consideration of other major risk factors. In contrast to the standard approach, same first treatment for all, treatment selection is tailored to an individual's risk. In patients with recent fractures of the spine, hip, or pelvis, fracture risk is very high and treatment should rapidly reduce that risk. For others, the target is a specific BMD level and should consider the likelihood that the treatment target can be attained within a reasonable period of time, which differs for osteoporosis medications. After initial therapy, BMD should be assessed to determine if the target has been achieved. If so, strategies should focus on maintaining BMD. If the target is not yet achieved, treatment should be intensified, or continued if it is already the most potent option. This position statement represents a consensus of expert recommendations about treatment targets and strategies to achieve those targets based on the best available evidence.

Official position of the Brazilian Association of Bone Assessment and Metabolism (ABRASSO) on the evaluation of body composition by densitometry: part I (technical aspects)-general concepts, indications, acquisition, and analysis.

OBJECTIVE: To review the technical aspects of body composition assessment by dual-energy X-ray absorptiometry (DXA) and other methods based on the most recent scientific evidence. MATERIALS AND METHODS: This Official Position is a result of efforts by the Scientific Committee of the Brazilian Association of Bone Assessment and Metabolism (Associação Brasileira de Avaliação Óssea e Osteometabolismo, ABRASSO) and health care professionals with expertise in body composition assessment who were invited to contribute to the preparation of this document. The authors searched current databases for relevant publications. In this first part of the Official Position, the authors discuss the different methods and parameters used for body composition assessment, general principles of DXA, and aspects of the acquisition and analysis of DXA scans. CONCLUSION: Considering aspects of accuracy, precision, cost, duration, and ability to evaluate all three compartments, DXA is considered the gold-standard method for body composition assessment, particularly for the evaluation of fat mass. In order to ensure reliable, adequate, and reproducible DXA reports, great attention is required regarding quality control procedures, preparation, removal of external artifacts, imaging acquisition, and data analysis and interpretation.

Challenges and opportunities for quality densitometry in Latin America.

Latin America and the Caribbean region account for 8% of the world's total population. Experts from 18 countries were invited to contribute to this article to provide the best available data on the number, types, and quality of densitometry, DXA experts, the local/national incidence and prevalence of osteoporosis and fragility fractures, and other uses and information on the challenges and opportunities for quality densitometry with examples of local initiatives. Osteoporosis is the primary reason for densitometry in our region, which is not a priority for public health in most countries. Access and quality are major challenges, and there is a clear trend to concentrate on densitometry services in the largest cities. Urgent action is needed to face the rapidly increasing burden of osteoporosis in our region, including robust and up to date epidemiology, access to health professionals, and quality densitometry. Health professionals require better access to training, courses, and other activities at a more local or regional level.

Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial.

BACKGROUND: Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. METHODS: We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov, NCT02782741. We report results of the 49-week primary analysis period. FINDINGS: Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI -0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]). INTERPRETATION: We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease. FUNDING: Sanofi Genzyme.

Efficacy and tolerability of once-monthly oral ibandronate (150 mg) and once-weekly oral alendronate (70 mg): additional results from the Monthly Oral Therapy With Ibandronate For Osteoporosis Intervention (MOTION) study.

BACKGROUND: The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention) study reported that once-monthly ibandronate was noninferior to once-weekly alendronate in terms of increasing bone mineral density (BMD) at the lumbar spine and total hip over 12 months. On analysis of secondary and exploratory end points in MOTION, which included trochanter and femoral neck BMD, monthly ibandronate was found to be noninferior to weekly alendronate. The coprimary, secondary, and exploratory BMD end points from MOTION have been previously reported. OBJECTIVE: This report presents additional results from the MOTION study, including response rates in terms of lumbar spine and total hip BMD gains above baseline; findings from a comparison of serum concentrations of bone turnover markers; and tolerability analysis, including adverse events that led to withdrawal and gastrointestinal (GI) adverse events. METHODS: MOTION was a 12-month (with 15-day follow-up), randomized, multinational, multicenter, double-blind, double-dummy, parallel-group, noninferiority study in postmenopausal women aged 55 to <85 years with osteoporosis. Patients were randomly assigned to receive 150-mg-monthly oral ibandronate and weekly alendronate-matched placebo, or 70-mg-weekly oral alendronate and monthly ibandronate-matched placebo, for 12 months. At baseline, day 7 of treatment, 3 and 6 months, 6 months + 7 days, and 12 months, serum concentrations of markers of bone resorption (C-telopeptide of the a chain of type 1 collagen [sCTX]) and bone formation (serum N-terminal propeptides of type 1 collagen) were measured in a subset of the total trial population. At baseline and month 12, BMD was measured using dual-energy x-ray absorptiometry. Exploratory analyses of patients whose spine, total hip, and trochanter BMD at 12 months were above baseline (responders) were also performed. RESULTS: A total of 1760 women were enrolled (ibandronate, 887 patients; alendronate, 873). The median changes in the trough concentrations of sCTX were -75.5% with monthly ibandronate and -81.2% with weekly alendronate. The percentage of patients with mean lumbar spine and total hip BMD gains above baseline (responders) were 90% and 87%, respectively, for ibandronate and 92% and 90%, respectively, for alendronate. GI adverse events were reported in

Efficacy and safety of evogliptin in the treatment of type 2 diabetes mellitus in a Brazilian population: a randomized bridging study.

BACKGROUND: Evogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO's clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg). METHODS: In this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12-baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was < - 0.5% (beneficial metabolic response). An analysis of covariance estimated the change in HbA1c and FPG adjusted by baseline HbA1c, FPG, body mass index (BMI) and study site. Response rates to treatment were also established. No between-group statistical comparisons were planned. RESULTS: HbA1c mean reductions were - 1.26% (90% CI - 1.7%, - 0.8%), - 1.12% (90% CI - 1.4%, - 0.8%), - 1.29% (90% CI - 1.6%, - 1.0%), and - 1.15% (90% CI - 1.5%, - 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of - 18.94 mg/dL, - 21.17 mg/dL, and - 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO's "target" dose (5 mg) was confirmed. No safety concerns were identified. CONCLUSIONS: These results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg).Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016).

Diagnosis and treatment of hypoparathyroidism: a position statement from the Brazilian Society of Endocrinology and Metabolism.

Objective To present an update on the diagnosis and treatment of hypoparathyroidism based on the most recent scientific evidence. Materials and methods The Department of Bone and Mineral Metabolism of the Sociedade Brasileira de Endocrinologia e Metabologia (SBEM; Brazilian Society of Endocrinology and Metabolism) was invited to prepare a document following the rules set by the Guidelines Program of the Associação Médica Brasileira (AMB; Brazilian Medical Association). Relevant papers were retrieved from the databases MEDLINE/PubMed, LILACS, and SciELO, and the evidence derived from each article was classified into recommendation levels according to scientific strength and study type. Conclusion An update on the recent scientific literature addressing hypoparathyroidism is presented to serve as a basis for the diagnosis and treatment of this condition in Brazil.

Corrigendum to "New and Emerging Therapies for Osteoporosis".

[This corrects the article DOI: 10.4061/2010/318320.].

Bone density testing in clinical practice.

The diagnosis of osteoporosis and monitoring of treatment is a challenge for physicians due to the large number of available tests and complexities of interpretation. Bone mineral density (BMD) testing is a non-invasive measurement to assess skeletal health. The "gold-standard" technology for diagnosis and monitoring is dual-energy X-ray absorptiometry (DXA) of the spine, hip, or forearm. Fracture risk can be predicted using DXA and other technologies at many skeletal sites. Despite guidelines for selecting patients for BMD testing and identifying those most likely to benefit from treatment, many patients are not being tested or receiving therapy. Even patients with very high risk of fracture, such as those on long-term glucocorticoid therapy or with prevalent fragility fractures, are often not managed appropriately. The optimal testing strategy varies according to local availability and affordability of BMD testing. The role of BMD testing to monitor therapy is still being defined, and interpretation of serial studies requires special attention to instrument calibration, acquisition technique, analysis, and precision assessment. BMD is usually reported as a T-score, the standard deviation variance of the patient's BMD compared to a normal young-adult reference population. BMD in postmenopausal women is classified as normal, osteopenia, or osteoporosis according to criteria established by the World Health Organization. Standardized methodologies are being developed to establish cost-effective intervention thresholds for pharmacological therapy based on T-score combined with clinical risk factors for fracture.

Update on osteoporosis therapy.

Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes a person to increased fracture risk. Fractures are often associated with increased morbidity, higher mortality, loss of function and even psychological consequences. Pharmacotherapeutic interventions (e.g., bisphosphonates, selective estrogen receptor modulators, calcitonin, and teriparatide) in women with postmenopausal osteoporosis provide substantial reduction in fracture risk over and above risk reduction with calcium and vitamin D supplementation alone. The importance of nutritional support along with an appropriate exercise regimen, avoiding smoking and excessive alcohol use is to be emphasized along with the pharmacologic approach to osteoporosis. Despite the effectiveness of therapy with pharmacologic agents, most patients who start therapy do not remain on treatment for more than 1 year.

Low bone mass in children and adolescents.

Osteoporosis is a disease characterized by low bone mass and micro architectural alterations of bone tissue leading to enhanced bone fragility and increased fracture risk. Although research in osteoporosis has focused mainly on the role of bone loss in the elderly population, it is becoming increasingly clear that the amount of bone that is gained during growth is also an important determinant of future resistance to fractures. Thus, considerable interest is being placed on defining preventive strategies that optimize the gain of bone mass during childhood and adolescence. Knowledge of the determinants accounting for the physiologic and genetic variations in bone accumulation in children will provide the best means toward the early diagnosis and treatment of osteoporosis. This article reviews the techniques available for bone mass measurements in children and the major determinants and diseases influencing bone accretion during childhood and adolescence.

Diagnosing vertebral fractures: missed opportunities.

Vertebral fractures are the single most common type of osteoporotic fracture. Postmenopausal women are at increased risk for osteoporotic vertebral fractures compared with women of childbearing age. Vertebral fractures are associated with an increase in morbidity, mortality, and high risk of a subsequent vertebral fracture, regardless of bone mineral density. Despite the common occurrence and serious consequences of vertebral fractures, they are often unrecognized or misdiagnosed by radiologists. Moreover, vertebral fractures may be described by variable terminology that can confuse rather than enlighten referring physicians. We conducted a survey of spine X-ray reports from a group of postmenopausal women screened for participation in a study of osteoporosis at Centro de Pesquisa Clínica do Brasil. A descriptive analysis evaluated the variability of reports in 7 patients. Four independent general radiologists issued reports assessing vertebral fractures through a blinded analysis. The objective of this study was to evaluate for consistency in these reports. The analysis found marked variability in the diagnosis of vertebral fractures and the terminology used to describe them. In community medical practices, such variability could lead to differences in the management of patients with osteoporosis, with the potential for undertreatment or overtreatment depending on clinical circumstances. Accurate and unambiguous reporting of vertebral fractures is likely to be associated with improved clinical outcomes.

Diagnosis and management of Paget's disease of bone.

OBJECTIVE: To conduct a literature review on the diagnosis and management of Paget's disease of bone. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society of Endocrinology and Metabolism (SBEM) as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including "D", are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. CONCLUSION: We present a scientific statement on Paget's disease of bone providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment.

Recommendations of the Brazilian Society of Endocrinology and Metabology (SBEM) for the diagnosis and treatment of hypovitaminosis D.

OBJECTIVE: The objective is to present an update on the diagnosis and treatment of hypovitaminosis D, based on the most recent scientific evidence. MATERIALS AND METHODS: The Department of Bone and Mineral Metabolism of the Brazilian Society of Endocrinology and Metabology (SBEM) was invited to generate a document following the rules of the Brazilian Medical Association (AMB) Guidelines Program. Data search was performed using PubMed, Lilacs and SciELO and the evidence was classified in recommendation levels, according to the scientific strength and study type. CONCLUSION: A scientific update regarding hypovitaminosis D was presented to serve as the basis for the diagnosis and treatment of this condition in Brazil.

Accelerated fracture healing with teriparatide.

Satisfactory healing of the osteoporotic fracture is critically important to functional recovery, morbidity, and quality of life. Some therapies for osteoporosis may affect the processes associated with bone repair. For example, bisphosphonates in experimental models are associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. For the osteoanabolic agent teriparatide, case reports and a randomized trial have produced mixed results, but they are consistent with a positive impact of teriparatide on fracture healing. Some of the agents currently being developed for osteoporosis, notably sclerostin and DKK1 antibodies have shown a beneficial effect on fracture healing. At this point, therefore, there is no evidence that osteoporosis therapies are detrimental to fracture healing with some promising experimental evidence for positive effects on healing, notably for those agents whose actions are primarily anabolic.