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Bones, Hormones & the Mitochondria

- when it comes to bone health they're all connected

3.6.22

Bone hormones - a complex web

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, with skeletal muscle also being an important component of bone health, with age-related degradation of muscle mass being a continuous process.

So many factors contribute to reduced bone quality – aging for one (tell me about it 🙄), medications, menopause (tell me about it again 🙄), and let’s not forget an inflamed, disrupted gut, poor liver/kidney function, and IR. But did you also know that a complex network of regulatory hormones modulate and support the skeletal system and bone health? The body’s hormones operate within a web of interconnection impacted by many factors, ultimately affecting the balance, function and health of body systems, and the skeletal system is no exception; multiple hormones modulate and support bone health - even gelding our boys can affect their bone health as it changes their sex hormones for a lower sex drive, aka hypogonadism.

Responding to changes in blood calcium and phosphorous levels, these regulatory hormones affect the formation and turnover of bone throughout the life stages, which makes supporting the lifelong bone remodeling process, maintaining or influencing bone homeostasis, essential for optimal bone health.

  • Parathyroid hormone (PTH) - this calcium-regulating hormone controls the level of calcium in the blood and stimulates both resorption and formation of bone.
  • Calcitriol (1,25 dihydroxy vitamin D) - also a noted calcium-regulating hormone, calcitriol is produced from vitamin D and is required for calcium absorption.
  • Calcitonin - calcitonin protects against excessive blood calcium levels during early life by inhibiting bone turnover and decreasing reabsorption.
  • Sex hormones - estrogen is a key regulator of bone remodeling, with testosterone important for skeletal growth.
  • Growth hormones - growth hormone and its production of the insulin-like growth factor (IGF-1) influences bone formation.
  • Thyroid hormones - these hormones are required for skeletal maturation and influence adult bone maintenance.
  • Cortisol - large amounts of this adrenal gland hormone block bone growth, with glucocorticoid-induced osteoporosis being the most common secondary cause of osteoporosis.
  • Insulin - important for bone growth, insulin signalling regulates both bone formation and resorption.
  • Leptin - this circulating hormone has direct and indirect influences on bone metabolism.

And then there's the mitochondria connection

The equine bone fragility syndrome (BFS) or silica-associated osteoporosis (SAO) is a chronic and progressive disorder of horses characterised by increased respiratory issues, exercise intolerance, skeletal deformation, lameness, stiffness, fractures, low bone mass and deterioration of bone tissue. Sarcopenia, aka muscle-wasting, is a progressive decline of muscle mass with loss of strength or physical performance, common in our senior horses that gradually results in overall weakness.

There’s now growing evidence indicating that both disorders share many common biological pathways – there’s even a newly identified age-related musculoskeletal syndrome termed 'osteosarcopenia', highlighting the pathologic connections between simultaneous bone and muscle disorders. It’s characterised by porous and fragile bone as well as low muscle mass and function, and can contribute to an increased risk of falls, fractures, and dare I say it, mortality.

So, it’s no surprise to learn that the body’s 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 bone and for optimal function of myocytes in muscle. A recent study focusing on mitochondrial performance suggests that mitochondrial dysfunction impairs bone formation (osteogenesis), increases osteoclast activity, and accelerates age-related bone loss.

Related to overall muscle aging, mitochondria are central regulators; specifically, the loss of mitochondrial integrity in myocytes has been recognised as a potential factor in age-related muscle degeneration.

Connecting Musculoskeletal & Mitochondrial Health

Senescence - the condition or process of deterioration with age; loss of a cell's power of division and growth.

Cellular senescence has been implicated in the progressive, age-related loss of function across various body tissues, including muscle and bone, and the quality of mitochondrial performance is a key component of senescence, with impaired energy metabolism and dysregulated mitochondrial homeostasis both contributing to the negative impact of senescence.

Which means … when we have sub-optimal mitochondrial quality and function, musculoskeletal health is negatively impacted:

  • Mitochondrial bioenergetics regulate stem cells in bone homeostasis, indicating that compromised energy metabolism and oxidative stress contribute to age-related stem cell dysfunction in bone.
  • Mitochondrial quality plays an important role in maintaining muscle health, with dysfunction linked to age-related muscle atrophy and sarcopenia.

Studies are now suggesting that specifically targeting mitochondrial health hold promise for improving musculoskeletal function during aging. A 2020 study also investigated the beneficial effect of the aforementioned butyrate on mitochondrial pathways and function, with results showing that butyrate promoted mitochondrial antioxidant enzymes and energy metabolism, preserved bone microstructure and calcium homeostasis, and activated bone metabolism, reversing bone loss. Yet more evidence as to why the cellulose fibre in stemmy hay is so crucial to provide the fibre necessary for the fermentation process of the hindgut and production of those all-important VFAs.

Lifestyle-based support

Lifestyle approaches can help restore hormonal balance - no surprise that an anti-inflammatory diet is a priority, hence avoiding ultra-processed feeds alongside stress management. In addition to a nutrient-dense diet, specific minerals and nutraceuticals help to positively impact bone density and quality - calcium and magnesium are vital, alongside vitamin D from the great outdoors, as it helps regulate the amount of calcium and phosphate in the body. Finally, ensuring the omega-3 EFAs are balanced to the levels in forage (all explained in our Linseed page).

Feeding the appropriate cellulose fibre (from hay) through the hindgut is crucial as well; as well as the hindgut biome producing the three volatile fatty acids – butyrate, acetate and proprionate – all naturally derived from the fibre fermentation that create the horse’s energy, compelling results from a 2020 animal study suggest that butyrate is required to stimulate bone formation and increase bone mass, highlighting the relationship between how maintaining a healthy gut microbiome optimises bone health.

And another No Surprise – exercise! Other studies have suggested that exercise increases levels of PGC-1alpha, which regulates mitochondrial biogenesis and reduces the loss of skeletal muscle mass through the PGC-1alpha/SIRT1 signaling pathway. In other words (and plainer English) exercise promotes the remodeling of muscle tissue. 😉 Apparently, endurance training is of particular benefit, as it improves energy metabolism, metabolic flexibility and muscle quality.

Additional therapies that may help enhance muscle strength include increasing quality protein - have a look at Agrobs’ MyoProtein Flakes or Simple Systems’ Sainfoin pellets – not alfalfa!.

Finally, and somewhat ironically, the use of Corticosteroids – the very drugs that are frequently prescribed to treat lameness - carry bone health risks. Always better to follow an anti-inflammatory diet and support with phytonutrients.

References

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