Sirimongkolchaiyakul Ornatcha, Pereira Renata C, Gales Barbara, Bacchetta Justine, Salusky Isidro B, Wesseling-Perry Katherine
Department of Pediatrics, David Geffen School of Medicine at UCLA, United States of America.
Department of Pediatrics, Faculty of Medicine, Vajira Hospital, Navamindrahiraj University, Thailand.
Bone Rep. 2021 Jul 8;15:101104. doi: 10.1016/j.bonr.2021.101104. eCollection 2021 Dec.
Bone marrow adiposity is associated with bone disease in the general population. Although chronic kidney disease (CKD) is associated with increased bone fragility, the correlation between marrow adiposity and bone health in CKD is unknown. We evaluated the relationship between bone marrow adipocytes and bone histomorphometry in 32 pediatric patients. We also evaluated the effects of growth hormone and calcitriol (1,25(OH)D)-two therapies commonly prescribed for pediatric bone disease-on marrow adiposity and bone histomorphometry. Finally, the adipogenic potential of primary human osteoblasts from CKD patients was assessed , both alone and in the presence of 1,25(OH)D. In cross-sectional analysis, marrow adipocyte number per tissue area (Adi.N/T.Ar) correlated with bone formation rate/bone surface (BFR/BS) in patients with high bone turnover (r = -0.55, p = 0.01) but not in those with low/normal bone turnover. Changes in bone formation rate correlated with changes Adi.N/T.Ar on repeat bone biopsy(r = -0.48, p = 0.02). , CKD and control osteoblasts had a similar propensity to transition into an adipocyte-like phenotype; 1,25(OH)D had very little effect on this propensity. In conclusion, marrow adiposity correlates inversely with bone turnover in pediatric patients with high turnover renal osteodystrophy. The range of adiposity observed in pediatric patients with low/normal bone turnover is not explained by intrinsic changes to precursor cells or by therapies but may reflect the effects of circulating factors on bone cell health in this population.
在普通人群中,骨髓脂肪过多与骨病相关。虽然慢性肾脏病(CKD)与骨脆性增加有关,但CKD患者骨髓脂肪过多与骨骼健康之间的相关性尚不清楚。我们评估了32例儿科患者骨髓脂肪细胞与骨组织形态计量学之间的关系。我们还评估了生长激素和骨化三醇(1,25(OH)D)——两种常用于治疗儿科骨病的疗法——对骨髓脂肪过多和骨组织形态计量学的影响。最后,评估了CKD患者原代人成骨细胞单独及在1,25(OH)D存在时的成脂潜能。在横断面分析中,高骨转换患者每组织面积的骨髓脂肪细胞数量(Adi.N/T.Ar)与骨形成率/骨表面(BFR/BS)相关(r = -0.55,p = 0.01),而低/正常骨转换患者则无此相关性。重复骨活检时骨形成率的变化与Adi.N/T.Ar的变化相关(r = -0.48,p = 0.02)。CKD和成骨细胞转变为脂肪细胞样表型的倾向相似;1,25(OH)D对此倾向影响甚微。总之,在高转换型肾性骨营养不良的儿科患者中,骨髓脂肪过多与骨转换呈负相关。低/正常骨转换儿科患者中观察到的脂肪过多范围,不能用前体细胞的内在变化或治疗来解释,而可能反映了循环因子对该人群骨细胞健康的影响。