Bone density and metabolism in subjects with microdeletion of chromosome 22q11 (del22q11).
BACKGROUND
Although hypoparathyroidism with hypocalcaemia is one of the most frequent clinical features of monoallelic microdeletion of chromosome 22q11 (22q11DS), bone mass and metabolism have not yet been assessed in these patients.


METHODS
This study aimed to evaluate bone mass and metabolism in a cohort of patients, both children and adults, with 22q11DS.


METHODS
In twenty-eight patients with 22q11DS (median age 12.5, range 6.1-42.8 years), serum levels of ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin and bone-specific alkaline phosphatase (BSAP), and urinary deoxypyridinoline concentrations were evaluated. In these patients, bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) examination, and volumetric BMD (bone mineral apparent density (BMAD)) was calculated. The data obtained from paediatric and adult patients were compared with two age-, sex- and body size-matched healthy subject control groups.


RESULTS
Patients with 22q11DS showed a reduced BMAD Z-score compared with controls (P<0.001). These patients also had significantly lower ionised (P<0.001) and total calcium (P<0.05) levels as well as lower PTH levels (P<0.05), compared with the controls. In particular, children and young patients with 22q11DS had significantly lower serum osteocalcin levels (P<0.001), BSAP levels (P<0.001) and urinary deoxypyridinoline concentrations (P<0.001) than controls. These results were not confirmed in adults. Finally, patients with hypoparathyroidism and/or hypocalcaemia at the time of the study showed significantly lower ionised (P<0.001) and total calcium levels (P<0.001), PTH levels (P<0.05), BSAP levels (P<0.001), osteocalcin levels (P<0.001) and urinary deoxypyridinoline concentrations (P<0.001), compared with patients without hypoparathyroidism and/or hypocalcaemia. Nonetheless, the BMAD Z-score did not show substantial differences between these two groups.


CONCLUSIONS
Subjects with 22q11DS have a significant reduction in bone mass that appears to be more severe in adults who have already attained peak bone mass than in children who are still growing. Therefore, we suggest a close monitoring of bone mass and metabolism in 22q11DS patients.
Department of Paediatrics, University of Florence, Florence, Italy. stefano.stagi@yahoo.it
Stefano
S
Stagi
Elisabetta
E
Lapi
Eleonora
E
Gambineri
Cristina
C
Manoni
Maurizio
M
Genuardi
Gloria
G
Colarusso
Camilla
C
Conti
Francesco
F
Chiarelli
Maurizio
M
de Martino
Chiara
C
Azzari
D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D002648:Child; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D014807:Vitamin D / Q000031:analogs & derivatives
D000596:Amino Acids; D010281:Parathyroid Hormone; D010710:Phosphates; D015675:Osteocalcin; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase; D002118:Calcium