RESUMO
Some studies based on bone biopsy have demonstrated that in patients with tumor-induced osteomalacia (TIO) the mineralization process of the bone matrix is profoundly disturbed. However, the interrelationship between clinical and biochemical features and bone microarchitecture in this disease needs further analysis. With this purpose in mind, we set out three objectives: (i) to determine bone microarchitecture and estimated bone strength in a group of patients with tumor-induced osteomalacia using high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA), (ii) to investigate correlations between duration of disease, biochemical features, bone density, HR-pQCT and FEA parameters, and (iii) to compare HR-pQCT and FEA parameters with a healthy control group. Ten patients with TIO were included. All patients had non-resolved disease. At the distal radius, all bone microarchitecture parameters were significantly affected in patients with TIO in comparison with healthy controls. At the distal tibia, all parameters were significantly impaired, except for trabecular thickness. All the parameters were more affected in the distal tibia than in the distal radius. Women with TIO (n = 7) had significantly lower bone strength parameters than healthy controls. In men (n = 3), bone strength parameters were significantly lower than in the control group at the distal tibia. Alkaline phosphatase levels exhibited a negative correlation with microarchitecture parameters, failure load, and stiffness. Higher levels of parathyroid hormone correlated with poorer microarchitecture parameters. We believe that in TIO, hormonal disturbances and the lack of mechanical stimulus specially converge to generate an extremely harmful combination for bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).
Assuntos
Densidade Óssea , Rádio (Anatomia) , Osso e Ossos/diagnóstico por imagem , Feminino , Humanos , Masculino , Osteomalacia , Síndromes Paraneoplásicas , Rádio (Anatomia)/diagnóstico por imagem , TíbiaRESUMO
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
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas do Fêmur/patologia , Pós-Menopausa , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
The purpose of the present study was to compare the clinical characteristics of "pure" uric acid (UA) stone formers with that of "pure" calcium oxalate (CaOx) stone formers and to determine whether renal handling of UA, urinary pH, and urinary excretion of promoters and inhibitors of stone formation were different between the two groups. Study subjects comprised 59 patients identified by records of stone analysis: 30 of them had "pure" UA stones and 29 had "pure" CaOx nephrolithiasis. Both groups underwent full outpatient evaluation of stone risk analysis that included renal handling of UA and urinary pH. Compared to CaOx stone formers, UA stone formers were older (53.3 +/- 11.8 years vs. 44.5 +/- 10.0 years; P = 0.003); they had higher mean weight (88.6 +/- 12.5 kg vs. 78.0 +/- 11.0 kg; P = 0.001) and body mass index (29.5 +/- 4.2 kg/m(2) vs. 26.3 +/- 3.5 kg/m(2); P = 0.002) with a greater proportion of obese subjects (43.3% vs. 16.1%; P = 0.01). Patients with "pure" UA lithiasis had significantly lower UA clearance, UA fractional excretion, and UA/creatinine ratio, with significantly higher serum UA. The mean urinary pH was significantly lower in UA stone formers compared to CaOx stone formers (5.17 +/- 0.20 vs. 5.93 +/- 0.42; P < 0.0001). Patients with CaOx stones were a decade younger, having higher 24-h urinary calcium excretion (218.5 +/- 56.3 mg/24 h vs. 181.3 +/- 57.1 mg/24 h; P = 0.01) and a higher activity product index for CaOx [AP (CaOx) index]. Overweight/obesity and older age associated with low urine pH were the principal characteristic of "pure" UA stone formers. Impairment in urate excretion associated with increased serum UA was also another characteristic of UA stone formers that resembles patients with primary gout. Patients with pure CaOx stones were younger; they had a low proportion of obese subjects, a higher urinary calcium excretion, and a higher AP index for CaOx.
Assuntos
Oxalato de Cálcio/metabolismo , Nefropatias/metabolismo , Nefrolitíase/metabolismo , Ácido Úrico/metabolismo , Adulto , Idade de Início , Oxalato de Cálcio/urina , Feminino , Humanos , Nefropatias/epidemiologia , Nefropatias/urina , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Ácido Úrico/urinaRESUMO
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
Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etiologia , Osso e Ossos/diagnóstico por imagem , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Absorciometria de Fóton , Adulto , Idoso , Densidade Óssea , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Although urine phosphate loss has been associated with hypercalciuria, it is debated how frequently renal phosphate leak is present in hypercalciuric patients. We reviewed the records of 100 consecutive adult patients who were diagnosed with idiopathic hypercalciuria and calcium urolithiasis, searching for the presence of renal phosphate leak. The renal phosphate threshold, normalized for the glomerular filtration rate (TmPO4/GFR), of the hypercalciuric patients followed a normal distribution and had a good correlation with serum phosphate ( r=0.77; p<0.0001). There were no correlations between TmPO4/GFR and urinary calcium or between serum phosphorus and urinary calcium. We found only nine patients (9%) with renal phosphate leak. These patients had a mean TmPO4/GFR of 2.19 mg% (0.70 mmol/l) and serum phosphorus of 2.65 mg% (0.85 mmol/l). Nevertheless, urinary calcium was not significantly different between patients with or without low TmPO4/GFR. We conclude that renal phosphate leak is an infrequent finding in patients with idiopathic hypercalciuria and is not associated with a higher urinary calcium loss.