Mineral and organic matrix composition at bone forming surfaces in postmenopausal women with osteoporosis treated with either teriparatide or zoledronic acid

Paschalis, Eleftherios P.; Dempster, David W.; Gamsjaeger, Sonja; Rokidi, Stamatia; Hassler, Norbert; Brozek, Wolfgang; Chan-Diehl, Faye W.; Klaushofer, Klaus; Taylor, Kathleen A.

Affiliations

¹Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria

²Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, NY, USA

³Department of Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY, USA

⁴Eli Lilly and Company USA, LLC, Indianapolis, IN, USA

Abstract and keywords

The ability of bone to resist fracture is dependent on the composite nature of its mineral and organic matrix content. Teriparatide (TPTD) and zoledronic acid (ZOL) are approved anabolic and antiresorptive therapies, respectively, to reduce fracture risk in women with postmenopausal osteoporosis. In the SHOTZ study, postmenopausal women with osteoporosis were treated with TPTD (20 μg daily, subcutaneous) or ZOL (5 mg/year, intravenous infusion) for 24 months. Iliac crest biopsies were obtained at 6 months and again at 24 months from approximately one third of the original study cohort. To investigate the early effects of these two drugs on the quality of newly formed bone, we used vibrational spectroscopic techniques to analyze tetracycline-labelled transiliac biopsies obtained from participants at the 6-month time point. Raman spectra were acquired at forming trabecular and intra-cortical surfaces (identified by fluorescent double labels), to determine mineral, organic matrix, glycosaminoglycan, and tissue water content, as well as mineral maturity/crystallinity at three specific tissue ages (1–5, 15, and ≥25 days). Fourier transformed infrared microspectroscopy was used to determine pyridinoline/divalent collagen cross-link ratios. At 6 months, treatment with TPTD versus ZOL resulted in lower mineral and higher organic matrix content, increased tissue water content, and lower mineral/matrix, mineral maturity/crystallinity, glycosaminoglycan content, and pyridinoline/divalent enzymatic collagen cross-link ratio.

Our results suggest that TPTD and ZOL have differential effects on material properties of newly formed bone at individual remodeling sites, highlighting their different mechanisms of action.

Keywords: Osteoporosis, bone matrix; Collagen; Matrix mineralization; Anabolics; Antiresorptives

Links

DOI: 10.1016/j.bone.2021.115848

PubMed: 33453443

WoS: 000623118400006

History

Received: 2020-07-7

Revised: 2021-01-12

Accepted: 2021-01-12

Online: 2021-01-14

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Cited By (1)

Year	Entry
2022	Paschalis E, Gamsjaeger S, Burr D. Bone quality in an ovariectomized monkey animal model treated with two doses of teriparatide for either 18 months, or 12 months followed by withdrawal for 6 months. Bone. May 2022;158:116366.