Assuntos

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We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high-resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten-free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone-specific parameters and CD serology) at both time points. Secondary, we compared 1-year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Compared with baseline, the trabecular compartment in the distal radius and tibia improved significantly (trabecular density, trabecular/bone volume fraction [BV/TV] [p < 0.0001], and trabecular thickness [p = 0.0004]). Trabecular number remained stable in both regions. Cortical density increased only in the tibia (p = 0.0004). Cortical thickness decreased significantly in both sites (radius: p = 0.03; tibia: p = 0.05). DXA increased in all regions (lumbar spine [LS], p = 0.01; femoral neck [FN], p = 0.009; ultradistal [UD] radius, p = 0.001). Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected for their age. © 2016 American Society for Bone and Mineral Research.

Assuntos

RESUMO

Reports of atypical femoral fractures (AFFs) in patients receiving long- term bisphosphonate therapy have raised concerns regarding the genesis of this rare event. Using high-resolution peripheral quantitative computed tomography (HR-pQCT), we conducted a study to evaluate bone microarchitecture in patients who had suffered an AFF during long-term bisphosphonate treatment. The aim of our study was to evaluate if bone microarchitecture assessment could help explain the pathophysiology of these fractures. We compared bone volumetric density and microarchitectural parameters measured by HR-pQCT in the radius and tibia in 20 patients with AFFs with 35 postmenopausal women who had also received long-term bisphosphonate treatment but had not experienced AFFs, and with 54 treatment-naive postmenopausal women. Control groups were similar in age, body mass index (BMI), and bone mineral density (BMD). Mean age of the 20 patients with AFFs was 71 years, mean lumbar spine T-score was -2.2, and mean femoral neck T-score was -2. Mean time on bisphosphonate treatment was 10.9 years (range, 5-20 years). None of the patients had other conditions associated with AFFs such as rheumatoid arthritis, diabetes or glucocorticoid use. There were no statistically significant differences in any of the parameters measured by HR-pQCT between postmenopausal women with or without treatment history and with or without history of atypical fractures. We could not find any distinctive microarchitecture features in the peripheral skeleton of women who had suffered an atypical fracture of the femur while receiving bisphosphonate treatment. This suggests that risk of developing an atypical fracture is not related to bone microarchitecture deterioration. Our results indicate that there may be other individual factors predisposing to atypical fractures in patients treated with bisphosphonates, and that those are independent of bone microarchitecture. In the future, identification of those factors could help prevent and understand the complex physiopathology of these rare events.

Assuntos

RESUMO

Denosumab is a fully human monoclonal antibody that inhibits the formation, function and survival of osteoclasts, preventing the interaction of tumor necrosis factor ligand superfamily member 11 (receptor activator of nuclear factor kappa-B ligand, RANKL) with the tumor necrosis factor receptor superfamily member 11A (osteoclast differentiation factor receptor, ODFR, receptor activator of NF-KB, RANK). This results in a reduction in bone resorption and an increase in bone mineral density. In clinical studies, denosumab has been shown to decrease the risk for vertebral, hip and nonvertebral fractures in women with postmenopausal osteoporosis and the risk for new vertebral fractures in men with nonmetastatic prostate cancer receiving androgen deprivation therapy, with a rate of side effects similar to placebo. A number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab is a new alternative for the prevention and treatment of postmenopausal osteoporosis and a promising agent for the treatment of other bone diseases associated with bone loss.

Assuntos

RESUMO

Denosumab is the first fully human monoclonal antibody that inhibits the formation, function, and survival of osteoclasts by blocking the interaction of receptor activator of nuclear factor-κB (RANK) ligand with its osteoclastic receptor RANK. Clinical studies have shown that the decreased bone resorption and increased bone mineral density resulting from the use of denosumab 60 mg twice yearly entail significant risk reduction of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis, with an acceptable rate of side effects so far. Following its approval by the US Food and Drug Administration and the European Medicines Agency, a number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab offers a new choice for the treatment of postmenopausal osteoporosis in patients at high risk for fracture.

Assuntos

RESUMO

OBJECTIVE: To determine the safety and efficacy of full-length parathyroid hormone, PTH(1-84), treatment for up to 36 months by evaluating bone mineral density (BMD) changes, bone histomorphometric indices, and clinical fracture incidence in postmenopausal women with osteoporosis. BACKGROUND: The TOP trial demonstrated increased lumbar spine BMD (6.9%) versus placebo after 18 months of PTH(1-84) treatment and reduced the incidence of new vertebral fractures (61%; p = 0.001). The therapeutic benefits of long-term treatment of postmenopausal women with PTH(1-84) are unknown. METHODS: The safety and efficacy of 36 months of once-daily dosing with 100 µg PTH(1-84) in postmenopausal women with osteoporosis were assessed. Women receiving placebo during the TOP trial were eligible for PTH(1-84) in the extension study. CLINICAL TRIAL REGISTRATION: NCT00172120. RESULTS: Lumbar spine BMD increased by 8.5% above baseline (p < 0.001) at 36 months of PTH(1-84) treatment, remaining stable during the last 12 months of treatment. Increases in total hip and femoral neck BMD occurred more slowly, reaching 3.2% and 3.4%, respectively above baseline at 36 months (p < 0.001). The total hip BMD showed no signs of reaching a limiting value although the femoral neck plateaued from months 24 to 36. Seven patients had vertebral fractures during the placebo phase of the TOP trial and before entering the extension study, but this rate decreased with the introduction of PTH(1-84) therapy, resulting in a single worsened vertebral fracture in the first 6 months and no further vertebral fractures from months 6 to 36. Treatment over 36 months with PTH(1-84) was well-tolerated and iliac crest biopsies showed no adverse effects on bone. LIMITATIONS: There was no placebo group for BMD comparisons. The number of patients assessed for fracture incidence was small. CONCLUSIONS: PTH(1-84) treatment for 36 months resulted in significant increases in BMD at the lumbar spine and hip, was associated with a lower incidence of vertebral fracture when compared to before therapy initiation, and was well-tolerated. The continuous increases in total hip BMD suggest that prolonged PTH(1-84) treatment may be beneficial for postmenopausal osteoporosis. Increased BMD at the femoral neck and lumbar spine also showed favourable changes but plateaued between 24 and 36 months. Long-term treatment was not associated with abnormalities in bone biopsies.

Assuntos

RESUMO

Peripheral quantitative computed tomography (pQCT) systems measure bone parameters noninvasively using low radiation doses. This limits image resolution but is practical for the diagnosis and quantitative monitoring of the properties of the peripheral human skeleton. pQCT determines volumetric bone mineral density separately in trabecular and cortical bone. It may combine densitometry determinations with geometric estimates and use strain-stress indexes, and it may be used to analyze muscle variables in some areas, allowing the study of regional fragility. Experimental and clinical ex vivo studies show that pQCT variables correlate with biomechanical predictors of fragility and/or fractures. Since pQCT was approved by the US Food and Drug Administration in 1997, new skeletal regions (human femur and mandible) have been considered in the development of the system. Basically, pQCT explores intraindividual and interindividual variations in greater detail and compares the impact of skeletal diseases, risk factors, and anabolic and catabolic treatments within a given bone cross section.

Assuntos

RESUMO

Several studies have suggested an increased prevalence of osteopenia in dialysis. Peripheral quantitative computed tomography (pQCT) is a new technique that allows the noninvasive evaluation of trabecular and cortical bone separately. The aim of the study was: (1) to evaluate cortical bone by pQCT in continuous ambulatory peritoneal dialysis (CAPD) patients and compare the data with that obtained in healthy controls; and (2) to correlate cortical bone parameters with bone mineral density (BMD) of the lumbar spine and femoral neck and total bone mineral content (TBMC). Cortical bone parameters were obtained in 22 CAPD patients and 27 healthy individuals at the distal radius using a Stratec XCT 960 pQCT machine. In the dialysis patients, we also determined BMD and TBMC by bone densitometry. Dialysis patients, compared with controls, showed a significant reduction in volumetric cortical BMD (VcBMD) (p = 0.04) and cortical thickness (cThk) (p < 0.0001) with a significant increase in radial total cross-sectional area (TA) (p = 0.006), endosteal circumference (p < 0.0001), and buckling ratio (p < 0.0001). In CAPD patients, total time on dialysis correlated negatively with radial total BMD (p < 0.01) and VcBMD (p < 0.01). Age correlated positively with TA (p < 0.01), endosteal (p < 0.01), and periosteal circumferences (p < 0.01). Serum intact parathyroid hormone (PTH) levels correlated positively with endosteal (p = 0.04) and periosteal perimeter (p = 0.01). Total alkaline phosphatase correlated negatively with VcBMD (p < 0.01), and positively with endosteal perimeter (p = 0.02). Total bone mineral content correlated significantly with radial cortical content (p < 0.001), cross-sectional cortical area (cA; p < 0.001), and cThk (p < 0.01) but not with total radial BMD, VcBMD, or buckling ratio. No correlations were found between radial cortical parameters and BMD measured at the lumbar spine or femoral neck. We conclude that dialysis patients show cortical osteopenia with marked cortical thinning partially mediated by PTH action on bone. Total bone mineral content correlated with various radial cortical parameters (content, area, and thickness) but not with others. No correlations were found between cortical bone parameters measured at the peripheral skeleton with areal bone density measured at the axial skeleton. These findings suggest that pQCT may be a new tool in the assessment of bone fragility in dialysis patients.

Assuntos

RESUMO

Osteoporosis-related fractures are a major public health problem worldwide. Antiresorptive drugs, which work principally by suppressing bone resorption, are the established therapeutic approach for the prevention of fragility fractures in patients with osteoporosis. Parathyroid hormone and its analogs represent a new class of agents with anabolic effects on the skeleton. The results of double-blind, randomized, placebo-controlled trials have shown that both the full length, 84 amino acid parathyroid hormone and teriparatide, the parathyroid hormone fragment (1-34) increase bone mineral density and reduce the risk of fracture when administered intermittently to postmenopausal osteoporotic women. Therefore, these drugs should be considered an alternative therapy in postmenopausal osteoporosis.

RESUMO

A 60-year-old Caucasian woman with a 1-year history of pain at the ribs, spine, and pelvis consulted at our Institute in March 1999. She brought a bone densitometry performed using a Lunar DPX densitometer that showed bone mineral density (BMD) measurements in the osteoporotic range at both the lumbar spine and the femoral neck. As a child she had had bowed legs and had been treated with ultraviolet radiation. Results of the laboratory test performed at our institute showed normal total serum calcium, repeated low serum P levels, and a low renal phosphate threshold with elevated total and bone fraction of alkaline phosphatase with normal intact parathyroid hormone (PTH). A diagnosis of hypophosphatemic osteomalacia due to renal phosphate leak was made. She began treatment with neutral sodium phosphate at 1.5 g/day and calcitriol 0.5 microg/day. Her serum P levels normalized, and there was a progressive decrease in alkaline phosphatase levels. The densitometry showed a very rapid increase in BMD values with normalization at the lumbar spine after 10 months of treatment. This case shows the importance of bone densitometry in the follow-up of patients with suspected osteomalacia.

Assuntos