Impact of Early Conventional Treatment on Adult Bone and Joints in a Murine Model of X-Linked Hypophosphatemia

被引:12
|
作者
Cauliez, Axelle [1 ,2 ,3 ]
Zhukouskaya, Volha V. [1 ,2 ,3 ,4 ,5 ,6 ]
Hilliquin, Stephane [1 ,2 ,3 ,7 ]
Sadoine, Jeremy [1 ,2 ,3 ]
Slimani, Lotfi [1 ,2 ,3 ]
Miceli-Richard, Corinne [7 ]
Briot, Karine [4 ,5 ,6 ,7 ]
Linglart, Agnes [4 ,5 ,6 ,8 ]
Chaussain, Catherine [1 ,2 ,3 ,4 ,5 ,6 ,9 ]
Bardet, Claire [1 ,2 ,3 ]
机构
[1] Univ Paris, Lab Orofacial Pathol Imaging & Biotherapies URP 2, Montrouge, France
[2] Univ Paris, FHU DDS Net, Dent Sch, Montrouge, France
[3] Plateforme Imagerie Vivant PIV, Montrouge, France
[4] Univ Paris Saclay, Univ Evry, INSERM, INTEGRARE,Genethon, Evry, France
[5] Hop Bicetre, Ctr Reference Malad Rares Metabolisme Calcium & P, Plateforme Expertise Malad Rares Paris Saclay, Filiere OSCAR,EndoRare, Le Kremlin Bicetre, France
[6] Hop Bicetre, BOND ERN, Le Kremlin Bicetre, France
[7] Univ Paris, Cochin Hosp, Dept Rheumatol, Paris, France
[8] Univ Paris Saclay, Hop Bicetre, AP HP, INSERM,U1185,Serv Endocrinol & Diabete Enfant,Ser, Le Kremlin Bicetre, France
[9] Bretonneau Hosp, AP HP, Reference Ctr Rare Disorders Calcium & Phosphate, Dent Med Dept,GHN, Paris, France
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 8卷
关键词
rickets; osteomalacia; Hyp mice; phosphorus; conventional treatment; XLH; PHEX; fibroblast growth factor 23;
D O I
10.3389/fcell.2020.591417
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
X-linked hypophosphatemia (XLH) is the most common form of genetic rickets. Mainly diagnosed during childhood because of growth retardation and deformities of the lower limbs, the disease affects adults with early enthesopathies and joint structural damage that significantly alter patient quality of life. The conventional treatment, based on phosphorus supplementation and active vitamin D analogs, is commonly administered from early childhood to the end of growth; unfortunately, it does not allow complete recovery from skeletal damage. Despite adequate treatment during childhood, bone and joint complications occur in adults and become a dominant feature in the natural history of the disease. Our previous data showed that the Hyp mouse is a relevant model of XLH for studying early enthesophytes and joint structural damage. Here, we studied the effect of conventional treatment on the development of bone and joint alterations in this mouse model during growth and young adulthood. Mice were supplemented with oral phosphorus and calcitriol injections, following two timelines: (i) from weaning to 3 months of age and (ii) from 2 to 3 months to evaluate the effects of treatment on the development of early enthesophytes and joint alterations, and on changes in bone and joint deformities already present, respectively. We showed that early conventional treatment improved bone microarchitecture, and partially prevented bone and joint complications, but with no noticeable improvement in enthesophytes. In contrast, later administration had limited efficacy in ameliorating bone and joint alterations. Despite the improvement in bone microarchitecture, the conventional treatment, early or late, had no effect on osteoid accumulation. Our data underline the usefulness of the Hyp murine model for preclinical studies on skeletal and extraskeletal lesions. Although the early conventional treatment is important for the improvement of bone microarchitecture, the persistence of osteomalacia implies seeking new therapeutic strategies, in particular anti-FGF23 approach, in order to optimize the treatment of XLH.
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页数:11
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