Bone material properties in premenopausal women with idiopathic osteoporosis

Barbara M. Misof, Sonja Gamsjaeger, Adi Cohen, Birgit Hofstetter, Paul Roschger, Emily Stein, Thomas L. Nickolas, Halley F. Rogers, David Dempster, Hua Zhou, Robert R. Recker, Joan M. Lappe, Donald McMahon, Eleftherios P. Paschalis, Peter Fratzl, Elizabeth Shane, Klaus Klaushofer

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.CaMean] and mode calcium concentration [Cn.CaMean] 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. © 2012 American Society for Bone and Mineral Research. ©

Original languageEnglish
Pages (from-to)2551-2561
Number of pages11
JournalJournal of Bone and Mineral Research
Volume27
Issue number12
DOIs
StatePublished - Dec 2012

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Osteoporosis
Bone and Bones
Minerals
Bone Density
Collagen
Physiologic Calcification
Fourier Analysis
Proteoglycans
Biopsy
Bone Matrix
Bone Remodeling
Hip Fractures
Osteoblasts
Osteogenesis
Catalytic Domain
Spine
Electrons
Calcium
Cancellous Bone

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Misof, B. M., Gamsjaeger, S., Cohen, A., Hofstetter, B., Roschger, P., Stein, E., ... Klaushofer, K. (2012). Bone material properties in premenopausal women with idiopathic osteoporosis. Journal of Bone and Mineral Research, 27(12), 2551-2561. https://doi.org/10.1002/jbmr.1699

Bone material properties in premenopausal women with idiopathic osteoporosis. / Misof, Barbara M.; Gamsjaeger, Sonja; Cohen, Adi; Hofstetter, Birgit; Roschger, Paul; Stein, Emily; Nickolas, Thomas L.; Rogers, Halley F.; Dempster, David; Zhou, Hua; Recker, Robert R.; Lappe, Joan M.; McMahon, Donald; Paschalis, Eleftherios P.; Fratzl, Peter; Shane, Elizabeth; Klaushofer, Klaus.

In: Journal of Bone and Mineral Research, Vol. 27, No. 12, 12.2012, p. 2551-2561.

Research output: Contribution to journalArticle

Misof, BM, Gamsjaeger, S, Cohen, A, Hofstetter, B, Roschger, P, Stein, E, Nickolas, TL, Rogers, HF, Dempster, D, Zhou, H, Recker, RR, Lappe, JM, McMahon, D, Paschalis, EP, Fratzl, P, Shane, E & Klaushofer, K 2012, 'Bone material properties in premenopausal women with idiopathic osteoporosis', Journal of Bone and Mineral Research, vol. 27, no. 12, pp. 2551-2561. https://doi.org/10.1002/jbmr.1699
Misof BM, Gamsjaeger S, Cohen A, Hofstetter B, Roschger P, Stein E et al. Bone material properties in premenopausal women with idiopathic osteoporosis. Journal of Bone and Mineral Research. 2012 Dec;27(12):2551-2561. https://doi.org/10.1002/jbmr.1699
Misof, Barbara M. ; Gamsjaeger, Sonja ; Cohen, Adi ; Hofstetter, Birgit ; Roschger, Paul ; Stein, Emily ; Nickolas, Thomas L. ; Rogers, Halley F. ; Dempster, David ; Zhou, Hua ; Recker, Robert R. ; Lappe, Joan M. ; McMahon, Donald ; Paschalis, Eleftherios P. ; Fratzl, Peter ; Shane, Elizabeth ; Klaushofer, Klaus. / Bone material properties in premenopausal women with idiopathic osteoporosis. In: Journal of Bone and Mineral Research. 2012 ; Vol. 27, No. 12. pp. 2551-2561.
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N2 - 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.CaMean] and mode calcium concentration [Cn.CaMean] 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. © 2012 American Society for Bone and Mineral Research. ©

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