Approaching virtual osteoid volume estimation and in-depth tissue characterization in patients with tumor-induced osteomalacia.

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.

Histomorphometric analysis of patients with femoral neck fracture and 25-hydroxyvitamin D deficiency: a cross-sectional study.

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.

Tumor mesenquimal fosfatúrico con rosetas gigantes: causa poco frecuente de osteomalacia oncogénica / Phosphaturic mesenchymal tumour with giant rosettes: a rare cause of oncogenic osteomalacia

El tumor mesenquimal fosfatúrico es una neoplasia rara que causa osteomalacia oncogénica por la fosfatonina FGF-23. Se describe el caso de una mujer que fue diagnosticada de osteomalacia oncogénica donde la tomografía computarizada reveló un tumor de tejidos blandos en el tórax. Una vez extirpado, fue identificado como tumor mesenquimal fosfatúrico tipo tejido conectivo mixto; se hizo revisión de la literatura y sus diagnósticos diferenciales. En este caso observamos rosetas gigantes, un hallazgo histológico no descrito antes(AU)

Phosphaturic mesenchymal tumour is a rare neoplasm which causes oncogenic osteomalacia due to the phosphatonin FGF-23. We report a case of a female patient crippled with oncogenic osteomalacia who was seen to have a soft tissue tumour of the thorax. The tumour was diagnosed as a phosphaturic mesenchymal tumour (mixed connective tissue variant). Giant rosettes were seen, a finding not previously reported. The differential diagnosis is discussed and the literature reviewed(AU)

Osteomalacia oncogénica por tumor mesenquimal fosfatúrico en fosa infratemporal / Oncogenic Osteomalacia due to Phosphaturic Mesenchymal Tumour in Infratemporal Fossa

La osteomalacia oncogénica es un síndrome infrecuente que se caracteriza por alteraciones en el metabolismo mineral producidas por la presencia de tumores fosfatúricos. La región de cabeza y cuello es la segunda localización más frecuente. Presentamos un caso de tumor mesenquimal fosfatúrico de fosa infratemporal que producía una osteomalacia oncogénica que se resolvió con la exéresis quirúrgica del mismo (AU)

Oncogenic osteomalacia is an uncommon syndrome characterized by phosphaturic tumours that produce mineral metabolism abnormalities. Head and neck is the second most frequent location of these tumours. We describe a case of a phosphaturic mesenchymal tumour in the infratemporal fossa that caused oncogenic osteomalacia, resolved by means of surgical excision (AU)

Defeito de mineralizaçäo e osteopenia em pacientes com espondilite anquilosante / Mineralization defect and osteopenia in patients with ankylosing spondylitis

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