Bone material properties in premenopausal women with idiopathic osteoporosis.
Idiopathic osteoporosis (IOP) in premenopausal women is characterized by fragility fractures at low or normal bone mineral density (BMD) in otherwise healthy women with normal gonadal function. Histomorphometric analysis of transiliac bone biopsy samples has revealed microarchitectural deterioration of cancellous bone and thinner cortices. To examine bone material quality, we measured the bone mineralization density distribution (BMDD) in biopsy samples by quantitative backscattered electron imaging (qBEI), and mineral/matrix ratio, mineral crystallinity/maturity, relative proteoglycan content, and collagen cross-link ratio at actively bone forming trabecular surfaces by Raman microspectroscopy and Fourier transform infrared microspectroscopy (FTIRM) techniques. The study groups included: premenopausal women with idiopathic fractures (IOP, n = 45), or idiopathic low BMD (Z-score ≤ -2.0 at spine and/or hip) but no fractures (ILBMD, n = 19), and healthy controls (CONTROL, n = 38). BMDD of cancellous bone showed slightly lower mineral content in IOP (both the average degree of mineralization of cancellous bone [Cn.Ca(Mean) ] and mode calcium concentration [Cn.Ca(Peak) ] are 1.4% lower) and in ILBMD (both are 1.6% lower, p < 0.05) versus CONTROL, but no difference between IOP and ILBMD. Similar differences were found when affected groups were combined versus CONTROL. The differences remained significant after adjustment for cancellous mineralizing surface (MS/BS), suggesting that the reduced mineralization of bone matrix cannot be completely accounted for by differences in bone turnover. Raman microspectroscopy and FTIRM analysis at forming bone surfaces showed no differences between combined IOP/ILBMD groups versus CONTROL, with the exceptions of increased proteoglycan content per mineral content and increased collagen cross-link ratio. When the two affected subgroups were considered individually, mineral/matrix ratio and collagen cross-link ratio were higher in IOP than ILBMD. In conclusion, our findings suggest that bone material properties differ between premenopausal women with IOP/ILBMD and normal controls. In particular, the altered collagen properties at sites of active bone formation support the hypothesis that affected women have osteoblast dysfunction that may play a role in bone fragility.
Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of Social Health Insurance Vienna (WGKK) and Austrian Social Insurance for Occupational Risk (AUVA) Trauma Centre Meidling, 1st Medical Department Hanusch Hospital, Vienna, Austria. barbara.misof@osteologie.at
Barbara M
BM
Misof
Sonja
S
Gamsjaeger
Adi
A
Cohen
Birgit
B
Hofstetter
Paul
P
Roschger
Emily
E
Stein
Thomas L
TL
Nickolas
Halley F
HF
Rogers
David
D
Dempster
Hua
H
Zhou
Robert
R
Recker
Joan
J
Lappe
Donald
D
McMahon
Eleftherios P
EP
Paschalis
Peter
P
Fratzl
Elizabeth
E
Shane
Klaus
K
Klaushofer
D000328:Adult; D015519:Bone Density; D001857:Bone Matrix / Q000503:physiopathology; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D050723:Fractures, Bone / Q000473:pathology; D006801:Humans; D015591:Microspectrophotometry; D008875:Middle Aged; D010006:Osteoblasts; D010012:Osteogenesis; D010024:Osteoporosis / Q000503:physiopathology*; D017697:Premenopause; D011446:Prospective Studies; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013752:Tetracycline
D013752:Tetracycline