Postmenopausal osteoporosis is a musculoskeletal disease with a common genetic trait which responds to strength training: a translational intervention study

Ole Kristoffer Olstad; Vigdis Teig Gautvik; Marissa LeBlanc; Karl Johnny Kvernevik; Tor Paaske Utheim; Anne Runningen; Håvard Wiig; Camilla Kirkegaard; Truls Raastad; Sjur Reppe; Kaare Morten Gautvik

doi:10.1177/1759720X20929443

Postmenopausal osteoporosis is a musculoskeletal disease with a common genetic trait which responds to strength training: a translational intervention study

Ther Adv Musculoskelet Dis. 2020 May 28:12:1759720X20929443. doi: 10.1177/1759720X20929443. eCollection 2020.

Affiliations

¹ Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
² Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway.
³ Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway.
⁴ Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway.
⁵ Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway, Beverly, MA, USA.
⁶ Lovisenberg Diakonale Sykehus, Unger-Vetlesen Institute, Lovisenberggata 17, Oslo 0456, Norway.

Abstract

Background: Clinical evidence suggests that body muscle mass is positively associated with bone mass, of significance for the elderly population at risk of osteoporosis (OP). Furthermore, muscle and bone interact mechanically and functionally, via local interactions as well as remotely via secreted components. Thus, it was of interest to compare muscle transcriptomes in postmenopausal OP and healthy women, and study effects of strength training on the muscle transcriptome, muscle stress proteins and bone mineral density (BMD).

Methods: Skeletal muscle histological and genetic properties were compared in postmenopausal healthy (n = 18) and OP (n = 17) women before and after heavy-load strength training for 13-15 weeks. The cohorts were of similar age and body mass index without interfering diseases, medication or difference in lifestyle factors. Muscle biopsies obtained before and after intervention were studied histologically, and stress proteins and transcriptomes analyzed.

Results: The OP women showed distinct muscle transcription profiles when compared with healthy women and had higher levels of the stress proteins HSP70 and α-β-crystalline. A set of 12 muscle transcripts, including ACSS3, FZD4, GNAI1 and IGF1, were differentially expressed before and after intervention (false discovery rate ⩽0.10, p ⩽0.001), and their corresponding bone transcripts were associated with BMD. Experimental data underline and describe the functionality of these genes in bone biology. OP women had 8% (p <0.01) higher proportion of type I fibres, but muscle fibre cross-sectional area did not differ. Muscle strength increased in both groups (p <0.01).

Conclusions: Postmenopausal healthy and OP women have distinct muscle transcriptomes [messenger ribonucleic acids (mRNAs) and microRNAs] that are modulated by strength training, translating into key protein alterations and muscle fibre changes. The function of common skeletal muscle and bone genes in postmenopausal OP is suggestive of a shared disease trait.

Keywords: heavy-load strength training; muscle biopsies; postmenopausal osteoporosis; transcriptional profiling.