Bone material properties in trabecular bone from human iliac crest biopsies after 3- and 5-year treatment with risedronate.
Long-term effects of risedronate on bone mineral maturity/crystallinity and collagen cross-link ratio in triple iliac crest biopsies of osteoporotic women were evaluated. In this double-blinded study, 3- and 5-year treatment with risedronate arrested the tissue aging encountered in untreated osteoporosis and in osteoporosis treated with other antiresorptives. This effect may be contributing to risedronate's antifracture efficacy.


BACKGROUND
Risedronate is widely used in the treatment of osteoporosis. It reduces bone turnover, increases BMD, and decreases fracture risk. To date, there are no data available on the long-term effects of risedronate on bone material properties in humans.


METHODS
Osteoporotic women enrolled in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects received calcium. They also received vitamin D supplementation if deficient at baseline. Triple iliac crest biopsies were collected from a subset of these subjects at baseline, 3 years, and 5 years. Mineral maturity/crystallinity and collagen cross-link ratio was measured in these biopsies using Fourier transform infrared imaging.


RESULTS
Patients that received placebo exhibited increased mineral maturity/crystallinity and collagen cross-link ratio after 3 and 5 years compared with baseline values. On the contrary, patients that received risedronate retained baseline values in both bone material indices throughout. A more spatially detailed analysis revealed that this was achieved mainly through beneficial effects on active bone-forming areas. Surprisingly, patients that received risedronate achieved premenopausal values at bone-forming areas in both indices after 5 years of treatment.


CONCLUSIONS
Long-term treatment with risedronate affects bone material properties (mineral maturity/crystallinity and collagen cross-link ratio) and arrests the tissue aging apparent in untreated osteoporosis. These changes at the material level of the bone matrix may contribute to risedronate's rapid and sustained antifracture efficacy in osteoporotic patients.
Durchschlag
Erich
E
Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna, Austria.
Paschalis
Eleftherios P
EP
Zoehrer
Ruth
R
Roschger
Paul
P
Fratzl
Peter
P
Recker
Robert
R
Phipps
Roger
R
Klaushofer
Klaus
K
D001706:Biopsy; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000627:therapeutic use; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007085:Ilium / Q000473:pathology*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D000068296:Risedronic Acid; D017550:Spectroscopy, Fourier Transform Infrared; D014807:Vitamin D / Q000627:therapeutic use
D050071:Bone Density Conservation Agents; D014807:Vitamin D; D003094:Collagen; D000068296:Risedronic Acid; D012968:Etidronic Acid; D002118:Calcium