Shwachman-Diamond syndrome is associated with low-turnover osteoporosis.
BACKGROUND
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency and bone marrow dysfunction. These result in malabsorption and hematological abnormalities. A skeletal dysplasia is also an integral feature of SDS. The present study assessed prevalence and determinants of osteopenia and osteoporosis in patients with SDS and disease-causing mutations in the SBDS gene.


METHODS
Eleven patients (8 males) aged from 5 to 37 years (median 16.7 years) with a genetically confirmed diagnosis of SDS were assessed for fracture history, bone mineral content (BMC), lean tissue mass (LTM) and bone mineral density (BMD) (Hologic Discovery A), osteoporotic vertebral changes, and for blood biochemistry and hematological parameters. Iliac crest bone biopsies were obtained from four patients for histology and histomorphometry.


RESULTS
The main findings were: (1) markedly reduced BMD Z-scores at the lumbar spine (median -2.1, range -4.4 to -0.8), proximal femur (median -1.3, range -2.2 to -0.7) and, whole body (median -1.0, range -2.8 to +0.6), and reduced Z-scores for height-adjusted BMC/LTM ratio (median -0.9, range -3.6 to +1.1); (2) vertebral compression fractures in three patients; and (3) blood biochemistry suggestive of mild vitamin D and vitamin K deficiency. Bone biopsies in four patients showed significant low-turnover osteoporosis with reduced trabecular bone volume, low numbers of osteoclasts and osteoblasts, and reduced amount of osteoid.


CONCLUSIONS
The results suggest that in addition to the skeletal dysplasia, SDS is associated with a more generalized bone disease characterized by low bone mass, low bone turnover and by vertebral fragility fractures. Osteoporosis may result from a primary defect in bone metabolism, and could be related to the bone marrow dysfunction and neutropenia.
Toiviainen-Salo
Sanna
S
Helsinki Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
Mäyränpää
Mervi K
MK
Durie
Peter R
PR
Richards
Nicole
N
Grynpas
Marc
M
Ellis
Lynda
L
Ikegawa
Shiro
S
Cole
William G
WG
Rommens
Johanna
J
Marttinen
Eino
E
Savilahti
Erkki
E
Mäkitie
Outi
O
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D011859:Radiography; D013577:Syndrome