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Review
. 2022 Jan 5;11(1):170.
doi: 10.3390/cells11010170.

Muscle and Bone Impairment in Infantile Nephropathic Cystinosis: New Concepts

Dieter Haffner  1   2 , Maren Leifheit-Nestler  1   2 , Candide Alioli  3 , Justine Bacchetta  3   4
Affiliations
Review

Muscle and Bone Impairment in Infantile Nephropathic Cystinosis: New Concepts

Dieter Haffner et al. Cells. .

Abstract

Cystinosis Metabolic Bone Disease (CMBD) has emerged during the last decade as a well-recognized, long-term complication in patients suffering from infantile nephropathic cystinosis (INC), resulting in significant morbidity and impaired quality of life in teenagers and adults with INC. Its underlying pathophysiology is complex and multifactorial, associating complementary, albeit distinct entities, in addition to ordinary mineral and bone disorders observed in other types of chronic kidney disease. Amongst these long-term consequences are renal Fanconi syndrome, hypophosphatemic rickets, malnutrition, hormonal abnormalities, muscular impairment, and intrinsic cellular bone defects in bone cells, due to CTNS mutations. Recent research data in the field have demonstrated abnormal mineral regulation, intrinsic bone defects, cysteamine toxicity, muscle wasting and, likely interleukin-1-driven inflammation in the setting of CMBD. Here we summarize these new pathophysiological deregulations and discuss the crucial interplay between bone and muscle in INC. In future, vitamin D and/or biotherapies targeting the IL1β pathway may improve muscle wasting and subsequently CMBD, but this remains to be proven.

Keywords: bone-muscle wasting; cysteamine; fibroblast growth factor 23; fractures; infantile nephropathic cystinosis; leptin; osteoclasts; sclerostin.

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Conflict of interest statement

D.H. received speaker fees and research grants from Horizon and Chiesi. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clinical presentation and causes of CMBD. Figure from Hohenfellner et al., with permission [18].
Figure 2
Figure 2
Serum levels of phosphate (A), calcium (B), intact parathyroid hormone (iPTH, (C)), and 1,25(OH)2D3 (D) in children with infantile nephropathic cystinosis (INC) and CKD controls as estimated glomerular filtration rate (eGFR) and after kidney transplantation (KTX). Gray box plots indicate INC patients; white box plots indicate CKD controls. Horizontal continuous and broken lines in (A) indicate the mean and upper and lower normal range; horizontal broken lines in (B,C) indicate the upper and lower normal range; horizontal broken lines in (D) indicate the PTH target range recommended by KDOQI; a, b, and c indicate p < 0.05, p < 0.01 and p < 0.001 versus healthy children, respectively. SDS, standard deviation score. Figure from Ewert et al., with permission [13].
Figure 3
Figure 3
Circulating levels of intact (A) and total (B) fibroblast growth factor 23, soluble Klotho (C), bone alkaline phosphatase (D), tartrate-resistant acid phosphatase 5b (E), osteoprotegerin (F) and sclerostin (G) in children with infantile nephropathic cystinosis (INC), and CKD controls at various stages of CKD and after kidney transplantation (KTX): Gray box plots indicate INC patients while white box plots indicate CKD controls. Horizontal continuous and broken lines indicate the mean, upper, and lower normal range; a, b, and c indicate p < 0.05, p < 0.01, and p < 0.001 versus healthy children, respectively. eGFR, estimated glomerular filtration rate (eGFR); SDS, standard deviation score; iFGF23, intact fibroblast growth factor 23; BAP, bone alkaline phosphatase; TRAP5b, tartrate-resistant acid phosphatase 5b; OPG, osteoprotegerin; sKlotho, soluble Klotho. Figure from Ewert et al. with permission [13].
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