João Lindolfo Cunha Borges

The Official Positions of the International Society for Clinical Densitometry: Indications of Use and Reporting of DXA for Body Composition

The technique of body composition by dual-energy X-ray absorptiometry (DXA) has been used for several years in the research environment. Its ability to accurately and precisely measure lean, fat, and mineral composition in various body compartments has been well validated. Furthermore, the technique is widely available to clinical patients on existing DXA instruments throughout the world through the use of specific software packages and scanning algorithms. There have been few clear statements regarding the clinical indications for body composition measurement in patients outside the research setting. This is in part because of the lack of specific documented interventions that would be affected by body composition test results, beyond usual clinical advice. We have examined a few of the most common, specific scenarios (HIV therapy, sarcopenia, bariatric surgery, obesity) and proposed indications for body composition assessment. We have also discussed contraindications to body composition testing.

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 <or=30% of patients per group during this 1-year study. CONCLUSION The data from these postmenopausal women with osteoporosis suggest that once-monthly 150-mg ibandronate therapy provided clinically comparable efficacy in terms of BMD response, reductions in bone turnover, and GI tolerability similar to that of weekly 70-mg alendronate.

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.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

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.

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.

Treinamento de força versus hidroginástica: uma análise transversal comparativa da densidade mineral óssea em mulheres na pós-menopausa

INTRODUCTION: Many studies have shown that resistance training has a positive effect on bone mineral density (BMD). However, few studies have compared the BMD of individuals undergoing resistance training and those training aquatic weight-bearing exercises. OBJECTIVE: To compare, in a cross-sectional study, the BMD of postmenopausal women undergoing resistance training and postmenopausal women training aquatic weight-bearing exercises. METHODS: The sample comprised 63 women divided into the following three groups: resistance training (STRENGTH: n = 15; 51.4 ± 2.7 years); aquatic weight-bearing exercises (WA-TER: n = 22; 54.5 ± 3.3 years); and non-trained controls (CONTROL: n = 26; 52.0 ± 3.3 years). All volunteers were on hormone replacement therapy for at least one year. The STRENGTH and WATER groups were training for at least one year prior to study beginning (mean years of training - STRENGTH: 4.5 ± 2.0; WATER: 4.2 ± 2.2). RESULTS: The STRENGTH group had higher BMD of total body, femoral neck, lumbar spine L2-L4 as compared with the CONTROL group (all P < 0.05). The WATER group had higher BMD of total body, total hip, lumbar spine L2-L4 as compared with the CONTROL group (all P < 0.05). However, no difference was observed between the STRENGTH and WATER groups regarding the sites assessed. CONCLUSIONS: Those findings suggest that not only the resistance training, but also aquatic weight-bearing exercises might be a non-pharmacological strategy to prevent BMD loss in postmenopausal women.

Densitometria clínica: posições oficiais 2006

We describe the official positions of the Brazilian Society for Clinical Densitometry (SBDens) for the performance and report of the bone mineral density testing. These positions were obtained by consensus in a meeting at Sao Paulo in 2006. SBDens positions were supported by other scientific societies described in the text.

New and emerging therapies for osteoporosis.

Osteoporosis is a common skeletal disease that increases the risk of fracture, with serious clinical and economic consequences. It can be diagnosed by dual-energy X-ray absorptiometry (DXA), even before a fracture has occurred, using the World Health Organization (WHO) criteria according to the patients T-score. The WHO has also developed a fracture risk assessment tool (FRAX) to estimate the 10-year probability of major osteoporotic fracture (clinical spine, hip, proximal humerus, and distal forearm) and hip fracture, using clinical risk factors for fracture and femoral neck bone mineral density (BMD), if available. Cost-effective pharmacological agents that have been proven to reduce fracture risk in patients at high risk for fracture are now widely available. However, despite great progress in the management of osteoporosis, it remains a disease that is underrecognized and undertreated; if treatment is started, persistence is often poor, with only about 50% of patients who are prescribed medication for osteoporosis still taking it 1 year later. Even when treatment is taken correctly and for a sufficient length of time for the patient to benefit from reduction in fracture risk, there may nevertheless be limitations in effectiveness (note the lack of evidence for reduction in the risk of hip fractures or other nonvertebral fractures with some agents), limitations in the duration of therapy (e.g., no more than 24 months of lifetime teriparatide in the US), and concerns regarding long-term safety, such as atypical femur fractures and osteonecrosis of the jaw with bisphosphonates. For all of these reasons, the goal of reducing the global burden of osteoporotic fractures is not being fully achieved. This special issue of the Journal of Osteoporosis describes new and emerging approaches to treatment that offer the potential to reduce the risk of fractures or manage their consequences better than what is currently observed in clinical practice. In recent years, our understanding of the pathophysiology of osteoporosis and the regulation of bone remodeling at the molecular level have undergone tremendous advances, leading to the investigation of drugs that target specific molecules in order to modulate the bone remodeling process. For example, the discovery that receptor activator of nuclear factor kappa B ligand (RANKL) is the principal regulator of osteoclastic bone resorption led to the development of denosumab, a fully human monoclonal antibody to RANKL. This potent antiresorptive agent, administered as a 60 mg subcutaneous injection every 6 months, recently received regulatory approval for the treatment of women with postmenopausal osteoporosis (PMO) at high risk for fracture. It has been shown to increase BMD, reduce bone turnover marker levels, and reduce the risk of vertebral fractures, hip fractures, and nonvertebral fractures in women with PMO. Wnt signaling initiated by the binding of Wnt proteins to the low density lipoprotein-related protein (LRP5/6)-frizzled receptor complex has recently been recognized as an important upregulator of osteoblastic bone formation; sclerostin and Dickkopf-1 (DKK-1) are natural inhibitors of Wnt signaling. In this issue, J. J. Mason and B. O. Williams describe a rare genetic disorder, sclerosteosis, resulting from a mutation of the SOST gene that encodes for sclerostin, and van Buchem disease, a related disorder caused by a mutation closely linked to SOST on chromosome 17q11.2. Patients with sclerosteosis and van Buchem disease have high bone mass due to downregulation of sclerostin, suggesting that a therapeutic agent that downregulates sclerostin in a controllable fashion might be a potent osteoanabolic treatment for patients with osteoporosis. Mason and Williams review many of the studies that have enhanced our understanding of the regulators of Wnt signaling and lead to the investigation of compounds with potential therapeutic applications through their effects on sclerostin or DKK1. A fascinating new finding, yet to be fully elucidated, is that serotonin produced by enterochromaffin cells in the duodenum also downregulates Wnt signaling, raising the possibility that modulation of serotonin production or activity might also be an effective treatment for patients with osteoporosis. In a related paper by S. Silverman in this issue, the preclinical and clinical studies of sclerostin inhibition are presented. The drugs used to treat osteoporosis are generally considered to be in 1 of 2 categories—antiresorptive (e.g, bisphosphonates) or osteoanabolic (e.g., teriparatide). Interestingly, some drugs may “uncouple,” at least in part, the closely related processes of bone resorption and formation. Strontium ranelate may be such a drug. Another, perhaps, is odanacatib, an investigational agent that inhibits cathepsin K, a protease produced by osteoclasts that is largely responsible for the degradation of the bone collagen matrix. J. L. Perez-Castrillon et al. review what is now known about the role of cathepsin K in health and disease, followed by data from phase 1 and phase 2 clinical trials with odanacatib. This drug is currently under investigation in a large phase 3 clinical trial to evaluate antifracture efficacy in women with PMO. Other papers in this issue cover new developments concerning skeletal heath in areas as diverse as bisphosphonate nanoparticles, melatonin, and thalassemia. The papers in the issue were selected from many excellent submissions. We give our thanks to all authors of these submissions and to the numerous reviewers who kindly donated their time and expertise in helping select and revise those published here. E. Michael Lewiecki Manuel Diaz Curiel Joao Lindolfo Borges Annie Kung Maria Luisa Brandi Hans Peter Dimai

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.

Resistance training versus weight-bearing aquatic exercise: a cross-sectional analysis of bone mineral density in postmenopausal women

INTRODUCTION Many studies have shown that resistance training has a positive effect on bone mineral density (BMD). However, few studies have compared the BMD of individuals undergoing resistance training and those training aquatic weight-bearing exercises. OBJECTIVE To compare, in a cross-sectional study, the BMD of postmenopausal women undergoing resistance training and postmenopausal women training aquatic weight-bearing exercises. METHODS The sample comprised 63 women divided into the following three groups: resistance training (STRENGTH: n = 15; 51.4 ± 2.7 years); aquatic weight-bearing exercises (WA-TER: n = 22; 54.5 ± 3.3 years); and non-trained controls ( CONTROL n = 26; 52.0 ± 3.3 years). All volunteers were on hormone replacement therapy for at least one year. The STRENGTH and WATER groups were training for at least one year prior to study beginning (mean years of training - STRENGTH: 4.5 ± 2.0; WATER: 4.2 ± 2.2). RESULTS The STRENGTH group had higher BMD of total body, femoral neck, lumbar spine L2-L4 as compared with the CONTROL group (all P < 0.05). The WATER group had higher BMD of total body, total hip, lumbar spine L2-L4 as compared with the CONTROL group (all P < 0.05). However, no difference was observed between the STRENGTH and WATER groups regarding the sites assessed. CONCLUSIONS Those findings suggest that not only the resistance training, but also aquatic weight-bearing exercises might be a non-pharmacological strategy to prevent BMD loss in postmenopausal women.