Bone Impairment in a Large Cohort of Chinese Patients With Tumor-Induced Osteomalacia Assessed by HR-pQCT and TBS.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density (aBMD) in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral (distal radius and tibia) and axial (lumbar spine) skeleton using high-resolution peripheral quantitative computed tomography (HR-pQCT) and trabecular bone score (TBS) and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry (DXA) or HR-pQCT scans were enrolled. Compared with age-, sex-, and body mass index (BMI)-matched healthy controls, TIO patients (n = 113) had lower volumetric BMD, damaged microstructure, and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS (<1.35) was higher than that with low L1 to L4 aBMD Z-score (Z ≤ -2) (43.9% versus 89.6%, p < 0.001). Higher intact fibroblast growth factor 23 (iFGF23), intact parathyroid hormone (iPTH), alkaline phosphatase, and β-isomerized C-terminal telopeptide of type I collagen (β-CTx) levels, more severe mobility impairment, and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection. © 2021 American Society for Bone and Mineral Research (ASBMR).

Ni X ，Feng Y ，Guan W ，Chi Y ，Li X ，Gong Y ，Zhao N ，Pang Q ，Yu W ，Wu H ，Huo L ，Liu Y ，Jin J ，Zhou X ，Lv W ，Zhou L ，Xia Y ，Liu W ，Jiajue R ，Wang O ，Li M ，Xing X ，Fukumoto S ，Jiang Y ，Xia W ... -  《-》

Shift in Calcium From Peripheral Bone to Axial Bone After Tumor Resection in Patients With Tumor-Induced Osteomalacia.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. After successful tumor resection, patients can recover from hypophosphatemia quicky. However, data on the changes in bone mineral density (BMD) and microstructure in the short term after surgery remained unclear. This work aimed to investigate the postoperative changes in BMD and microstructure both in peripheral and axial bone in TIO patients. We evaluated BMD and microarchitecture in 22 TIO patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy x-ray absorptiometry (DXA) before and 3 months after surgery in this retrospective study. In this study, a total of 22 TIO patients who had recovered serum phosphate levels postoperatively were enrolled. After surgery, areal BMD (aBMD) increased by 21.6% in the femoral neck, by 18.9% in the total hip, and by 29.5% in the lumbar spine. Moreover, TBS increased by 14.1% (all P < .001). In contrast, trabecular or cortical volumetric BMD (vBMD), and microstructure of trabecular bone (trabecular number, separation and bone volume ratio) and cortical bone (cortical thickness and porosity) at the distal radius or tibia were further deteriorated. Correlation analyses found that changes in femoral neck and total hip aBMD were both conversely associated with changes in trabecular vBMD and bone volume ratio, while positively correlated with change in trabecular separation at the distal radius. Although aBMD and microstructure in the axial bone were improved, vBMD and microstructure in the peripheral bone were further impaired shortly after surgery. Correlation of improvement of aBMD in the total hip and femoral neck with deterioration of vBMD and microstructure at the distal radius indicated a shift in calcium from the peripheral bone to the axial bone in the short term after tumor resection in TIO patients.

Ni X ，Zhang Z ，Guan W ，Chi Y ，Li X ，Gong Y ，Pang Q ，Yu W ，Wu H ，Huo L ，Liu Y ，Jin J ，Zhou X ，Lv W ，Zhou L ，Xia Y ，Liu W ，Jiajue R ，Cui L ，Wang O ，Li M ，Xing X ，Jiang Y ，Xia W ... -  《-》

Bone microstructure evaluated by TBS and HR-pQCT in Chinese adults with X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Although generalized mineralization defects have been observed, elevated areal bone mineral density (aBMD) in the lumbar spine measured by dual-energy X-ray absorptiometry (DXA) has also been found in XLH. In contrast, high-resolution peripheral quantitative computed tomography (HR-pQCT) revealed lower volumetric BMD (vBMD) and damaged bone microstructure in the peripheral bone in XLH. Trabecular bone score (TBS), which can assess the trabecular microstructure in the lumbar spine, has not been explored in XLH. This study aimed to explore TBS and its correlations with biochemical indices and HR-pQCT parameters in adult XLH patients. A total of 66 patients with XLH (26 men and 40 women) aged 29.6 ± 9.6 years and 66 age- and sex-matched healthy controls were included. Z score of lumbar spine aBMD was relatively high [2.0 (0.6, 3.7)], with normal TBS (1.475 ± 0.129) in the XLH patients. HR-pQCT revealed larger total and trabecular area in the peripheral bone in the XLH group compared with the control group. In addition, lower trabecular and cortical vBMD, lower trabecular number with greater separation, and lower bone strength at both the radius and tibia were found in the XLH group compared with the control group. Smaller cortical area, lower thickness and higher porosity in the XLH group compared with controls were only found at the radius. TBS was not associated with any biochemical indices, while better HR-pQCT parameters correlated with higher serum phosphate and lower ALP levels. TBS was positively related with aBMD but not HR-pQCT parameters. In conclusion, adult patients with XLH had high bone mass and normal TBS in the lumbar spine but compromised microarchitecture and bone strength in the peripheral bone. This finding indicated a site-specific effect of the disease on the skeleton in the XLH patients.

Ni X ，Guan W ，Pang Q ，Jin C ，Gong Y ，Liu W ，Wang O ，Li M ，Xing X ，Yu W ，Jiang Y ，Xia W ... -  《-》

Impaired bone mineral density and microarchitecture in female adolescents with IgE-mediated cow's milk allergy.

This study compared the bone parameters of adolescents with persistent cow's milk allergy (CMA) with those of healthy adolescents. Adolescents with CMA had compromised bone parameters (lower bone mineral density, impaired trabecular microarchitecture, and lower bone strength). Partial exclusion diet was associated with better bone parameters than total exclusion diet. Persistent immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) may impair bone parameters and increase the risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a novel methodology that not only assesses trabecular and cortical bone compartments and volumetric density measurements, but also evaluates bone microarchitecture and estimates biomechanical properties through finite element analysis (FEA). Both HR-pQCT and bone strength parameters derived from FEA have shown a strong correlation with fracture risk. To assess the bone density, microarchitecture, and bone strength of adolescents with persistent IgE-mediated CMA (IgE-CMA). This was an observational, cross-sectional study with female adolescents with persistent IgE-CMA and healthy control participants matched by female sex and sexual maturation. Bone parameters were assessed by areal bone mineral density (aBMD) through dual-energy X-ray absorptiometry (DXA), bone microarchitecture by HR-pQCT at the radius and tibia, and laboratory markers related to bone metabolism. The median age of adolescents with persistent IgE-CMA (n = 26) was 13.0 years (interquartile range (IQR) 11.4-14.7) and of healthy control participants (n = 28) was 13.6 years (IQR 11.9-14.9). Adolescents with IgE-CMA ingested 27.4% less calcium (p = 0.012) and 28.8% less phosphorus (p = 0.009) than controls. Adolescents with IgE-CMA had lower bone mineral content (BMC) (38.83 g vs. 44.50 g) and aBMD (0.796 g/cm2 vs. 0.872 g/cm2) at lumbar spine, and lower BMC (1.11 kg vs. 1.27 kg) and aBMD (0.823 g/cm2 vs. 0.877 g/cm2) at total body less head (TBLH) (p < 0.05). However, Z-scores BMC and Z-scores aBMD at lumbar spine and TBLH, when adjusted for Z-score height/age, were not significantly different between the groups. Moreover, CMA adolescents had lower bone strength at the distal tibia (S 169 kN/mm vs. 194 kN/mm; F Load 8030 N vs. 9223 N) (p < 0.05). Pairing of groups by the presence of menarche showed compromised parameters at the tibia-lower total volumetric BMD (Tt.vBMD) (293.9 mg HA/cm3 vs. 325.9 mg HA/cm3) and trabecular vBMD (Tb.vBMD) (170.8 mg HA/cm3 vs. 192.2 mg HA/cm3), along with lower cortical thickness (Ct.th) (1.02 mm vs. 1.16 mm) and bone strength (S 174 kN vs. 210 kN; F Load 8301 N vs. 9950 N)-and at the radius (S 61 kN/mm vs. 71 kN/mm; F Load 2920 N vs. 3398 N) (p < 0.05) among adolescents with IgE-CMA. Adolescents with IgE-CMA on a total exclusion diet (n = 12) showed greater impairment of bone features than those on a partial exclusion diet (n = 14), with lower lumbar spine Z-score BMC (- 0.65 vs. 0.18; p = 0.013), lumbar spine trabecular bone score (TBS) (1.268 vs. 1.383; p = 0.005), Z-score TBS (0.03 vs. 1.14; p = 0.020), TBLH Z-score BMC (- 1.17 vs. - 0.35; p = 0.012), TBLH Z-score aBMD (- 1.13 vs. - 0.33; p = 0.027), Tt.vBMD at the tibia (259.0 mg HA/cm3 vs. 298.7 mg HA/cm3; p = 0.021), Ct.th at the tibia (0.77 mm vs. 1.04 mm; p = 0.015) and Ct.th at the radius (0.16 mm vs. 0.56 mm; p = 0.033). Adolescents with persistent IgE-CMA had lower aBMD and compromised microarchitecture (impaired trabecular microarchitecture and lower bone strength). Adolescents on a partial exclusion diet had better bone parameters than those on a total exclusion diet.

Yonamine GH ，Domiciano DS ，Takayama L ，Castro APBM ，Pereira RMR ，Pastorino AC ... -  《-》

Microarchitectural parameters and bone mineral density in patients with tumour-induced osteomalacia by HR-pQCT and DXA.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic condition characterised by decreased tubular phosphate reabsorption. The purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in six TIO patients, compared with 18 healthy controls. Volumetric BMD and microarchitecture were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and areal BMD by dual-energy X-ray absorptiometry (DXA). Differences between groups were significant for p < .05. All TIO subjects were healthy until the development of diffuse bone pain and multiple skeletal fractures and deformities. At baseline, sPi and TmPi/GFR were low and patients were on vitamin D and phosphate replacement at the study. Compared with controls, TIO patients had lower aBMD at lumbar spine and hip, and lower vBMD at trabecular, cortical and entire bone, at distal radius (R) and distal tibia (T): trabecular vBMD (R = 118.3 × 177.1; T = 72.3 × 161.3 gHA/cm3 ); cortical vBMD (R = 782.3 × 866.5; T = 789.1 × 900.9 gHA/cm3 ); total region vBMD (R = 234.5 × 317; T = 167.1 × 295.8 gHA/cm3 ). Bone microarchitecture was very heterogeneous among patients and significantly different from controls: lower cortical thickness (R = 0.59 × 0.80; T = 0.90 × 1.31 mm), bone volume-to-total volume ratio (R = 0.09 × 0.14; T = 0.06 × 0.13) and Tb.N (R = 1.46 × 2.10; T = 0.93 × 1.96 mm-1 ) and also higher Tb.Sp (R = 0.70 × 0.41; T = 1.28 × 0.45 mm) and Tb.1/N.SD (R = 0.42 × 0.18; T = 0.87 × 0.20 mm). In this original study of TIO patients, DXA and HR-pQCT evaluation identified lower areal and volumetric BMD and severely impaired microarchitecture at cortical and trabecular bones, which probably contribute to bone fragility and fractures.

Mendes DAB ，Coelho MCA ，Gehrke B ，de Pinho LKJ ，Cardoso Lima LF ，Paranhos-Neto F ，de Mendonça LMC ，Farias MLF ，Madeira M ... -  《-》