Assuntos
Osso e Ossos , Osteomalacia , Humanos , Osteomalacia/patologia , Osso e Ossos/patologia , BiópsiaRESUMO
Tumor-induced osteomalacia (TIO) poses a significant diagnostic challenge, leading to increased disease duration and patient burden also by missing clinical suspicion. Today, diagnosis of osteomalacia relies on invasive iliac crest biopsy, if needed. Therefore, a noninvasive method would be beneficial for patients with severe osteomalacia, such as TIO, to inform their clinical management and address specific needs, like estimating the regeneration capacity at high osteoid volumes (OVs) or the potential of a hungry bone syndrome after tumor removal. Furthermore, given the lack of comprehensive histological characterization of TIO, there is a need for additional tissue characterization. Therefore, our assessment encompassed iliac crest biopsies that were examined using quantitative electron backscattered microscopy, Raman spectroscopy, micro-computed tomography, and histology to analyze the biopsy tissue. Our clinical assessment encompassed DXA and high-resolution peripheral quantitative computed tomography (HR-pQCT) alongside with biochemical analyses and clinical evaluations. Combining imaging and clinical data, we established a model to predict the OV. We compared 9 TIO patients with 10 osteoporosis (OPO) patients and 10 healthy controls. Histological analyses confirmed a pronounced OV in TIO patients (OPO: 1.20% ± 1.23% vs TIO: 23.55% ± 12.23%, P < .0005), and spectroscopy revealed lower phosphate levels in TIO biopsies. By combining HR-pQCT and laboratory diagnostics, we developed a linear regression model to noninvasively predict the OV revealing significantly higher modeled OV/BVmodel values of 24.46% ± 14.22% for TIO compared to the control group (5.952% ± 3.44%, P ≤ .001). By combining laboratory diagnostics, namely, ALP and Tt.BMDRadius measured by HR-pQCT, we achieved the calculation of the virtual osteoid volume to bone volume ratio (OV/BVmodel) with a significant correlation to histology as well as reliable identification of TIO patients compared to OPO and control. This novel approach is potentially helpful for predicting OV by noninvasive techniques in diagnostic procedures and improving the clinical management of TIO.
Osteomalacia, a bone mineralization disease, results in soft bones due to a lack of calcium or phosphate. Tumor-induced osteomalacia (TIO) is an acquired and challenging form of osteomalacia due to low serum phosphate levels that often lead to prolonged patient suffering. Current diagnosis of osteomalacia involves surgical bone biopsies, but a noninvasive approach would be beneficial, improving clinical management and addressing specific needs like estimating the bone's quality and ability to recover. We used advanced techniques like electron microscopy, spectroscopy, and high-resolution CT to study bone samples from 9 TIO patients. Additionally, we assessed their bone health through sophisticated imaging and blood analyses. Microscopy confirmed huge amounts of soft bone tissue due to a severe mineralization defect. By combining imaging and blood analysis, we developed a noninvasive method to predict the amount of soft tissue (osteoid) to understand soft bones without the need for surgical interventions. In conclusion, our innovative approach, combining blood diagnostics (alkaline phosphatase) with total BMD from high-resolution 3D clinical imaging of the lower arm, allows us to predict the osteoid amount virtually. This method can also compare TIO patients with controls or those with osteoporosis and might be helpful in the future.
Assuntos
Osteomalacia , Humanos , Osteomalacia/diagnóstico por imagem , Osteomalacia/patologia , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Síndromes Paraneoplásicas/diagnóstico por imagem , Síndromes Paraneoplásicas/patologia , Idoso , Ílio/patologia , Ílio/diagnóstico por imagemRESUMO
INTRODUCTION: Vitamin D deficiency causes osteoporosis, bone mineralization disorders, and osteomalacia. Osteomalacia is diagnosed using blood biochemical tests, clinical symptoms, and imaging; however, accurate detection of mineralization disorders requires tissue observation. We investigated the prevalence of bone mineralization disorders and their relationship with serum 25-hydroxyvitamin D (25OHD) levels in patients with untreated osteoporosis with femoral neck fractures. MATERIALS AND METHODS: A non-demineralized specimen was prepared from the femoral head removed during surgery in 65 patients. Bone histomorphometry of cancerous bone in the femoral head center was conducted. Osteoid volume per bone volume (OV/BV) and osteoid thickness (O.Th) were measured as indicators of mineralization disorder. RESULTS: The mean serum 25OHD level (11.9 ± 5.7 ng/mL) was in the deficiency range (< 12 ng/mL). There were no clinically diagnosed cases of osteomalacia (OV/BV > 10% and O.Th > 12.5 µm); however, one case of mineralization disorder, considered histologically pre-osteomalacia (OV/BV > 5% and O.Th < 12.5 µm), was observed (OB/BV, 17.6%; O.Th, 12.3 µm). Excluding this case, those with severe (25OHD < 12 ng/mL, at risk of osteomalacia; n = 39) and non-severe deficiency (25OHD ≥ 12 ng/mL; n = 25) did not significantly differ in OV/BV (%; 0.77 ± 0.54 vs. 0.69 ± 0.38, p = 0.484) or O.Th (µm; 5.32 ± 1.04 vs. 5.13 ± 0.78, p = 0.410). Further, 25OHD and OV/BV were not significantly correlated (R = - 0.124, p = 0.327). CONCLUSION: This is the first study in the twenty-first century to examine serum 25OHD concentrations and bone mineralization disorders in Japanese patients with osteoporosis. The results indicate that vitamin D deficiency does not necessarily cause bone mineralization disorders and rarely leads to osteomalacia.
Assuntos
Fraturas do Colo Femoral , Osteomalacia , Osteoporose , Deficiência de Vitamina D , Vitamina D/análogos & derivados , Humanos , Estudos Transversais , Osteomalacia/patologia , Densidade Óssea , Calcifediol , Deficiência de Vitamina D/complicações , Cabeça do Fêmur/patologiaRESUMO
Säo paucas as referências na literatura descrevendo aspectos histológicos e histomorfométricos no tecido ósseo de pacientes com espondilite anquilosante. O objetivo deste trabalho foi o estudo dos aspectos anatomopatológicos do tecido ósseo de pacientes com espindilite anquilosante, utilizando-se biópsia óssea de osso näo descalcificado. Dezesseis homens, brancos, com espondilite anquilosante, média de idade de 34 ñ 12 anos (15 a 55 anos) e tempo médio de doença de 11 ñ 8 anos (6 meses a 27 anos) submeteram-se à biópsia de crista iliaca. Quatorze pacientes apresentaram osteopenia em graus variáveis, dez com defeito de mineralizaçäo e três com osteomalacia. As correlaçöes, estatisticamente significantes, do tempo de evoluçäo da doença com o volume osteóide absoluto e relativo sugerem que a doença seja fator importante na determinaçäo da osteopenia e defeito de mineralizaçäo. Os autores concluíram que osteopenia e defeito de mineralizaçäo podem ser detectados precocemente em pacientes comn espondilite anquilosante e, conseqüentemente, podem e deveriam ser tratados