Treatment of postmenopausal osteoporosis patients with teriparatide for 24 months reverts forming bone quality indices to premenopausal healthy control values

Paschalis, Eleftherios P.<sup>1</sup>; Gamsjaeger, Sonja<sup>1</sup>; Klaushofer, Klaus<sup>1</sup>; Shane, Elizabeth<sup>2</sup>; Cohen, Adi<sup>3</sup>; Stepan, Jan<sup>4</sup>; Pavo, Imre<sup>5</sup>; Eriksen, Erik F.<sup>6,7</sup>; Taylor, Kathleen A.<sup>5</sup>; Dempster, David W.<sup>8,9</sup>

Affiliations

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

²Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Cente, New York, NY, USA

³Early Onset Osteoporosis Center, Metabolic Bone Diseases Program, Division of Endocrinology, Department of Medicine, Columbia University, College of Physicians & Surgeons, New York, NY, USA

⁴Institute of Rheumatology, Faculty of Medicine 1, Charles University, Prague, Czech Republic

⁵Eli Lilly and Company USA, LLC, Indianapolis, IN, USA

⁶Department of Endocrinology, Pilestredet Park Specialist Center, Oslo, Norway

⁷The Faculty of Dentistry, University of Oslo, Oslo, Norway

⁸Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, NY, USA

⁹Department of Pathology and Cell Biology, College of Physicians and Surgeons of Columbia University, New York, NY, USA

Abstract and keywords

Postmenopausal osteoporosis (PMOP) therapies are frequently evaluated by bone mineral density (BMD) gains against patients receiving placebo (calcium and vitamin D supplementation, a mild bone turnover-suppressing intervention), which is not equivalent to either healthy or treatment-naive PMOP.

The aim of the present observational study was to assess the effects of TPTD treatment in PMOP (20 μg, once daily) at 6 (TPTD 6m; n = 28, age 65 ± 7.3 years), and 24 (TPTD 24m; n = 32, age 67.4 ± 6.15 years) months on bone quality indices at actively forming trabecular surfaces (with fluorescent double labels). Data from the TPTD-treated PMOP patients were compared with those in healthy adult premenopausal women (HC; n = 62, age 40.5 ± 10.6 years), and PMOP receiving placebo (PMOP-PLC; n = 94, age 70.6 ± 4.5 years). Iliac crest biopsies were analyzed by Raman microspectroscopy at three distinct tissue ages: mid-distance between the second label and the bone surface, mid-distance between the two labels, and 1 μm behind the first label. Mineral to matrix ratio (MM), mineral maturity/crystallinity (MMC), tissue water (TW), glycosaminoglycan (GAGs), and pyridinoline (Pyd) content were determined. Outcomes were compared by ANCOVA with subject age and tissue age as covariates, and health status as a fixed factor, followed by Sidak's post-hoc testing (significance assigned to p < 0.05).

Both TPTD groups increased MM compared to PMOP-PLC. While TPTD 6m had values similar to HC, TPTD 24m had higher values compared to either HC or TPTD 6m. Both TPTD groups had lower MMC values compared to PMOP-PLC and similar to HC. TPTD 6m patients had higher TW content compared to HC, while TPTD 24m had values similar to HC and lower than either PMOP-PLC or TPTD 6m. Both TPTD groups had lower GAG content compared to HC group, while TPTD 6m had higher values compared to PMOP-PLC. Finally, TPTD 6m patients had higher Pyd content compared to HC and lower compared to PMOP-PLC, while TPTD 24m had lower values compared to PMOP-PLC and TPTD 6m, and similar to HC group.

The results of the present study indicate that effects of TPTD on forming trabecular bone quality indices depend on treatment duration. At the recommended length of 24 m, TPTD restores bone mineral and organic matrix quality indices (MMC, TW, Pyd content) to premenopausal healthy (HC) levels.

Keywords: Bone quality; Bone formation; Postmenopausal osteoporosis; Teriparatide; Human iliac crest biopsies; Raman spectroscopy

Links

DOI: 10.1016/j.bone.2022.116478

PubMed: 35779845

WoS: 000826578400001

History

Received: 2022-05-11

Revised: 2022-06-24

Accepted: 2022-06-27

Online: 2022-06-29

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