Bone Status in a Patient with Insulin-Like Growth Factor-1 Receptor Deletion Syndrome: Bone Quality and Structure Evaluation Using Dual-Energy X-Ray Absorptiometry, Peripheral Quantitative Computed Tomography, and Quantitative Ultrasonography

Abstract

Haploinsufficiency of the insulin-like growth factor (IGF)-1 receptor (IGF1R) gene is a rare, probably under-diagnosed, cause of short stature. However, the effects of IGF1R haploinsufficiency on glucose metabolism, bone status, and metabolism have rarely been investigated. We report the case of a patient referred to our center at the age of 18 months for short stature, failure to thrive, and Silver–Russell-like phenotype. Genetic analysis did not show hypomethylation of the 11p15.5 region or uniparental disomy of chromosome 7. Growth hormone (GH) stimulation tests revealed GH deficiency, whereas IGF-1 was 248 ng/mL. r-hGH treatment showed only a slight improvement (from −4.4 to −3.5 SDS). At 10 years of age, the child was re-evaluated: CGH-array identified a heterozygous de novo 4.92 Mb deletion in 15q26.2, including the IGF1R gene. Dual-energy X-ray absorptiometry showed a normal bone mineral density z-score, while peripheral quantitative computed tomography revealed reduced cortical and increased trabecular elements. A phalangeal bone quantitative ultrasonography showed significantly reduced amplitude-dependent speed of sound and bone transmission time values. The changes in bone architecture, quality, and metabolism in heterozygous IGF1R deletion patients, support the hypothesis that IGF-1 can be a key factor in bone modeling and accrual.

Pathophysiology and treatment of osteoporosis: challenges for clinical practice in older people

“…It has been hypothesised that a rise in IGF-1 during puberty results in increased plasma inorganic phosphate and calcitriol, leading to increased bone mass gain during puberty. Patients with haploinsufficiency of IGF-1 receptor have been found to have undesirable changes to bone architecture in accordance with this hypothesis [ 30 , 31 ]. Other factors that can influence peak bone mass include nutrition (calcium and vitamin D status), physical activity, inter-current illness and socioeconomic deprivation.…”

SUMO1 modification of IGF-1R combining with SNAI2 inhibited osteogenic differentiation of PDLSCs stimulated by high glucose

“…In recent years, the role of IGF-1R in osteogenesis and bone reconstruction has received increasing attention. Recent studies have shown that IGF-1R could be involved in alterations in blood glucose levels and bone metabolism [ 36 , 37 ] and interfered with the osteogenesis-related Wnt/β-catenin signaling pathway [ 38 , 39 ]. It has also been shown in animal experiments that IGF-1R and phosphorylation of IGF-1R were also significantly higher in OVX + streptozotocin-induced osteoporosis model rats than in normal rats [ 34 ].…”

SUMO1 modification of IGF-1R combining with SLUG inhibited osteogenic differentiation of PDLSCs stimulated by high glucose

“…Recent studies have shown that IGF-1R can be involved in alterations in blood glucose levels and bone metabolism [28,29] and interferes with the osteogenesis-related Wnt/β-catenin signaling pathway [30,31]. It has also been shown in animal experiments that IGF-1R expression levels and phosphorylation levels of IGF-1R are also signi cantly higher in OVX + streptozotocin-induced osteoporosis model rats than in normal rats [26].…”