The Bone and Mitochondria Connection

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Bone is a living tissue that not only mechanically supports the body and protects vital organs, but also produces blood cells, stores minerals, and impacts endocrine regulation. As a result of aging, hormonal imbalances, nutrient deficiencies/insufficiencies, or the frequent use of certain medications, the bone remodeling cycle may become unbalanced, with bone resorption rates outpacing formation. Per recent statistics, the prevalence of osteoporosis at either the femoral neck, lumbar spine, or both among US adults aged 50 or older is 12.6%, while prevalence of low bone mass (i.e., osteopenia, a precursor for osteoporosis) for the same population is 43.1%.1 An important component of bone health is skeletal muscle. Additionally, age-related degradation of muscle mass is a continuous process, with some studies suggesting a reduction in lean muscle starting as early as age 30.2

Bone-Muscle Unit: Crosstalk, Osteosarcopenia, & the Role of Mitochondria

Evolving research supports the concept of the bone-muscle unit that engages in a crosstalk that involves molecules secreted by both tissues working together toward homeostasis.3,4 While osteoporosis is characterized by low bone mass and deterioration of bone tissue, sarcopenia is a progressive decline of muscle mass with loss of strength or physical performance. Growing evidence indicates that both disorders share many common biological pathways.3,4 In fact, the newly identified age-related musculoskeletal syndrome termed “osteosarcopenia” highlights the pathologic connections between simultaneous bone and muscle disorders. Osteosarcopenia is characterized by porous and fragile bone as well as low muscle mass and function4,5 and contributes to an increased risk of falls, fracture, and mortality.6

Mitochondria play an essential role in the health of the bone-muscle unit. Mitochondrial function and quantity are important in the maintenance of osteoblasts and osteoclasts in bone7 and for optimal function of myocytes in muscle.8 A recent animal study focusing on mitochondrial performance suggests that mitochondrial dysfunction impairs osteogenesis, increases osteoclast activity, and accelerates age-related bone loss.9 Related to overall muscle aging, mitochondria are central regulators.2 Specifically, the loss of mitochondrial integrity in myocytes has been recognized as a potential factor in age-related muscle degeneration.8

To address musculoskeletal health as we age, can optimizing mitochondrial function positively impact both bone quality and muscle mass or even reverse age-related bone and muscle disorders.

Connecting Musculoskeletal & Mitochondrial Health

Cellular senescence has been implicated in the progressive, age-related loss of function across various body tissues, including muscle and bone,10 and the quality of mitochondrial performance is a key component of senescence.8 Impaired energy metabolism and dysregulated mitochondrial homeostasis contribute to the negative impact of senescence. Senescent cells accumulate dysfunctional mitochondria, increasing reactive oxygen species (ROS) production.10,11 In addition, while continuing research will help to elucidate the exact mechanisms involved, mitophagy, the selective cellular recycling of mitochondria more generally known as autophagy, is reduced in senescent cells.11

In the described environment of sub-optimal mitochondrial quality and function, musculoskeletal health is negatively impacted. For example:

  • Mitochondrial bioenergetics and quality control systems regulate stem cells in bone homeostasis. Increasing evidence indicates that compromised energy metabolism and oxidative stress contribute to age-related stem cell dysfunction in bone.12
  • Mitophagy is suggested to play a vital role in the proliferation, differentiation, and function of osteoblasts and osteoclasts. Dysregulation of mitophagy may promote damaged mitochondria and potentially induce apoptosis of osteoblasts or osteoclastogenesis in bone disorders.7
  • Mitochondrial quality plays an important role in maintaining muscle health. Dysfunctional mitophagy, increased ROS production, reduced mitochondrial biogenesis, and increased mitochondrial apoptotic susceptibility are all potentially linked to age-related muscle atrophy and sarcopenia.2

Animal studies suggest that treatments specifically targeting mitochondrial dysfunction hold promise for improving musculoskeletal function during aging.10 A 2020 animal study investigated the beneficial effect of sodium butyrate, a representative short-chain fatty acid, on mitochondrial pathways and function.13 Results indicated that the sodium butyrate promoted mitochondrial antioxidant enzymes and energy metabolism, preserved bone microstructure and calcium homeostasis, and activated bone metabolism, reversing bone loss.13 Other studies have suggested that exercise increases levels of PGC-1alpha, which regulates mitochondrial biogenesis and attenuates the loss of skeletal muscle mass through the PGC-1alpha/SIRT1 signaling pathway.14

Clinical Applications

Lifestyle treatment strategies help to support musculoskeletal health. Research studies suggest that an anti-inflammatory diet,15 exercise,16 and supplements such as omega-3 fatty acids17 and probiotics18,19 may positively impact bone density and quality. Recommended therapeutic approaches for patients with sarcopenia include appropriate exercise interventions that help to attenuate muscle loss and rebuild muscle mass.20,21 Additional treatment components that enhance muscle strength may include increased quality proteins22 and vitamin D23 or omega-3 fatty acid24 supplementations. Targeting mitochondrial dysfunctions and boosting mitochondrial health through lifestyle treatments may also help to address both bone and muscle disorders.

Therapeutic food plans such as IFM’s Mitochondrial Food Plan use nutrition to support mitochondrial biogenesis for improved energy production. In addition, studies suggest that intermittent fasting routines, if appropriate for a patient’s personalized nutrition strategy, may positively impact mitochondrial function, enhancing energy metabolism and overall health.25,26 Exercise is another therapeutic approach to support mitochondria, promoting increased mitochondrial content, improving respiratory capacity of each mitochondrion, and reducing ROS production.27 A 2021 review investigated how different exercise modalities potentially reverse age-related changes in skeletal muscle mitochondria.28 The review found that endurance and resistance training separately and combined have suggested benefit for mitochondrial aging and muscle disorders.28 Specifically:

  • Resistance training maintains and improves mobility, strength, and movement, preserving skeletal muscle function.28
  • Endurance training improves energy metabolism, metabolic flexibility, and muscle quality.28
  • Combined training may combine these noted benefits to bolster mitochondrial performance and quality to preserve the energetic and functional health of aging skeletal muscle.28

Research on how mitochondrial function impacts musculoskeletal health and the aging process continues to evolve. Learn more about optimizing mitochondria through personalized treatment strategies at IFM’s Bioenergetics Advanced Practice Module (APM).

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