Uncovering the bone-muscle interaction and its implications for the health and function of older adults (the wellderly project): Protocol for a randomized controlled crossover trial

Cassandra Smith, Xuzhu Lin, David Scott, Tara C. Brennan-Speranza, Ahmed Al Saedi, Alba Moreno-Asso, Mary Woessner, Ebrahim Bani Hassan, Nir Eynon, Gustavo Duque, Itamar Levinger

Research output: Contribution to journalArticleOtherpeer-review

8 Citations (Scopus)


Background: Bone and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. Objective: The proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. Methods: A total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press; one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. Results: The trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. Conclusions: This study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions.

Original languageEnglish
Article numbere18777
Number of pages15
JournalJMIR Research Protocols
Issue number4
Publication statusPublished - Apr 2021


  • Acute exercise
  • Adult
  • Aging
  • Bone
  • Clinical trial
  • Muscles
  • Osteocalcin
  • Progenitor cells
  • Sarcopenia
  • Stem cells

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