High bone turnover and accumulation of osteoid in patients with neurofibromatosis 1.
Although it is known that neurofibromatosis 1 (NF1) patients suffer from vitamin D deficiency and display decreased bone mineral density (BMD), a systematic clinical and histomorphometrical analysis is absent. Our data demonstrate that NF1 patients display high bone turnover and accumulation of osteoid and that supplementation of vitamin D has a beneficial effect on their BMD.


BACKGROUND
Neurofibromatosis 1 results in a wide range of clinical manifestations, including decreased BMD. Although it has been reported that NF1 patients have decreased vitamin D serum levels, the manifestation of the disease at the bone tissue level has rarely been analyzed.


METHODS
Thus, we performed a clinical evaluation of 14 NF1 patients in comparison to age- and sex-matched control individuals. The analysis included dual X-ray absorptiometry osteodensitometry, laboratory parameters, histomorphometric and quantitative backscattered electron imaging (qBEI) analyses of undecalcified bone biopsies.


RESULTS
NF1 patients display significantly lower 25-(OH)-cholecalciferol serum levels and decreased BMD compared to control individuals. Histomorphometric analysis did not only reveal a reduced trabecular bone volume in biopsies from NF1 patients, but also a significantly increased osteoid volume and increased numbers of osteoblasts and osteoclasts. Moreover, qBEI analysis revealed a significant decrease of the calcium content in biopsies from NF1 patients. To address the question whether a normalization of calcium homeostasis improves BMD in NF1 patients, we treated four patients with cholecalciferol for 1 year, which resulted in a significant increase of BMD.


CONCLUSIONS
Taken together, our data provide the first complete histomorphometric analysis from NF1 patients. Moreover, they suggest that low vitamin D levels significantly contribute to the skeletal defects associated with the disease.
Center for Biomechanics & Skeletal Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. s.seitz@uke.uni-hamburg.de
S
S
Seitz
C
C
Schnabel
B
B
Busse
H U
HU
Schmidt
F T
FT
Beil
R E
RE
Friedrich
T
T
Schinke
V F
VF
Mautner
M
M
Amling
D015502:Absorptiometry, Photon / Q000379:methods; D000328:Adult; D000368:Aged; D001706:Biopsy; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D016723:Bone Remodeling / Q000502:physiology*; D002112:Calcifediol / Q000097:blood; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000627:therapeutic use; D005260:Female; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D007085:Ilium / Q000473:pathology; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D010024:Osteoporosis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000209:etiology; D055815:Young Adult
D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D010710:Phosphates; D002762:Cholecalciferol; D002112:Calcifediol; D002118:Calcium