This nineteenth-century formulation describes how activity builds bone. A century later, it stands in its original form — despite the many biological studies aimed at proving, disproving, or modifying it. Why is this so?

The answer reflects the interplay between bone and muscle (i.e. “muscle-bone crosstalk”) and sheds light on osteosarcopenia, a debilitating condition that largely goes underreported and undertreated. Exploring this topic reveals strategies you can share with your patients to help them improve their bone density and muscle mass.

Osteosarcopenia is a new term that represents a frail subset of the elderly population that is affected by the hazardous duet of both osteoporosis and sarcopenia.¹

Osteosarcopenia is especially common after age 65 due to a progressive decline in muscle mass (~1% per year) and bone mineral density (BMD) (~1–1.5% per year).² Those who have this condition are at significantly higher risk of falls, fractures, and hospitalizations than others who have only osteoporosis or sarcopenia.

In fact, a study of 316 elderly Chinese adults found that 10.4% of men and 15.1% of women were osteosarcopenic. And the odds of frailty were significantly higher in osteosarcopenic patients compared to osteoporotic or sarcopenic patients alone.³

In many cases, osteosarcopenia is asymptomatic. But a previous history of falls and/or fractures in older people may indicate the presence of osteosarcopenia.

Since osteosarcopenia represents the combined effects of osteoporosis and sarcopenia, it can be helpful to pay attention to the risk factors for both of these conditions, which include: ⁴

• older age
• female
• high alcohol intake
• oral glucocorticoids
• menopause (females)
• low protein intake
• low BMI
• current smoking
• low dietary calcium
• low serum vitamin D
• hypogonadism (in men)
• hyperparathyroidism
• obesity
• rheumatoid arthritis
• living in residential aged-care facilities
• chronic kidney disease
• low mobility and function

With that being said, this field is still in its infancy. Almost all the research brings up hints rather than conclusions. So we’ll stick to a few well-documented effects of a few substances — the ones that give us some guidance in our diets and lives.

But first, we’ll need a little help from Wolff’s law.

Now that we’ve had a refresher on Wolff’s law, let’s look at three of the better understood components of muscle-bone crosstalk (osteocalcin, myostatin, and sclerostin). Hidden in this crosstalk are the underpinnings of Wolff’s law.

But first, apologies that much of this information comes from animal studies. Yes, the field is that new. But it’s old enough that multiple studies confirm that mouse DNA acts very much like human DNA.¹² As with humans, every substance they secrete has built-in checks and balances.

Osteocalcin (OCN) comes from osteoblasts (bone-building cells) in three forms: carboxylated, undercarboxylated, and non-carboxylated. For our purposes, the under- and non-carboxylated forms are the most important.

These forms enhance muscle contraction causing the muscles’ fibers to grow and multiply rapidly. As a result, muscular decline reverses — even in 15-month-old mice (probably the equivalent of a 51-year-old person).^7-12

What’s more, the undercarboxylated OCN prods pancreatic beta cells to release insulin, which goes back and helps the bones’ metabolism. Further, the carboxylated OCN prompts the hypothalamus to promote sympathetic (fight-or-flight) responses.

While all this is going on, insulin prompts the body’s fat cells to release leptin. This is the check and balance action that makes the brainstem secrete serotonin, putting reins on the hypothalamus’s sympathetic tone.

Often billed as rivals, osteocytes and osteoclasts (the cells resorbing the matrix of bone) work together in this. Once considered the enemy of bone strengthening, bone resorption raises active OCN levels. And osteoclasts that decarboxylate OCN make it active — another check and balance.

According to Wolff’s law, this is nature’s shrewd way of limiting and coordinating the entire process of remodeling bone. What’s more, OCN (coming from the bone) is more than overheard by many other parts of the body. It exerts a positive influence on cognition, memory (it works on the hippocampus), and male fertility. Moreover, OCN reduces heart disease and goes some distance toward preventing diabetes type II.^{25 26}

So we know that OCN is good for us. But how do we increase the number of molecules of OCN coursing through our systems?

• Vitamin K Supplementation (especially K2): It has a direct effect on osteocytes and stimulates OCN production.
• Weight Loss: Shedding extra pounds frees the hormone and hormone-like substances in muscles, bones, and fat cells that stimulate OCN.
• Exercise: Along with contributing to weight loss, exercising also helps improve bone density and muscle strength. One exercise shown to build bone density is yoga. (See details on my twelve-pose yoga sequence). Encourage your patients to add this to their exercise routine to give their bones and OCN levels the boost they need.¹³

A second part of the muscle-bone crosstalk involves myostatin. Myostatin is a member of the transforming growth factor beta (TGF-β) superfamily which inhibits skeletal muscle growth. It also has effects on bones and tendons.¹⁴

Specifically, myostatin keeps the muscles under lock and key, reducing their mass. Androgen (a male hormone) decreases myostatin. In addition, exercise lowers myostatin, prompting the muscles to grow in volume and strength.

This also makes for the enlargement and strengthening of the parts of bone that muscles attach to. In this way, myostatin helps shape and remodel bone.

Finally, a third part of the muscle-bone crosstalk involves sclerostin. Sclerostin is a small protein expressed by the SOST gene. It reduces osteoblastic bone formation.¹⁵

As such, it’s an important regulator of bone remodeling. It also assists in the crosstalk that shapes the large hip bone and wrist.

As with osteoporosis and sarcopenia, there are lifestyle changes your patients can make to help keep osteosarcopenia in check.

As mentioned earlier, regular exercise is key to having healthy bones and muscles. It has many positive effects on the older population, with one meta-analysis finding exercise reduced overall fracture risk by 51% in adults over 45 years old. ¹⁶

Moreover, exercise programs are even effective for frailer adults, with a meta-analysis of elderly residents in long-term care demonstrating a 29% reduced risk of falls in those that underwent combined resistance and balance training programs. ¹⁷

The current recommended daily allowance (RDA) for protein intake is 0.8 grams per kg of body weight. ²³ But this RDA was set over a decade ago, and experts now believe it’s not an adequate amount. More recent research recommends that older adults consume 1–1.5 grams of protein per kg of body weight.

Research shows that those who have osteosarcopenia are at significantly higher risk of falls, fractures, and hospitalizations than others who only have osteoporosis or sarcopenia. As with osteoporosis and sarcopenia, your patients can make certain lifestyle changes to help keep osteosarcopenia at bay.

For one, your patients can take Vitamin K, especially K2. It stimulates OCN production.

Another way to boost OCN levels is to lose weight. Doing so will free the hormone and hormone-like substances in muscles and bones that stimulate OCN.

As you know, a great way to lose weight is to exercise. In addition to helping your patients stay in shape, exercising also helps improve bone density and muscle strength. Moreover, exercise lowers myostatin, prompting the muscles to grow in volume and strength.

So, if your patients aren’t already, consider recommending that they add a twelve-pose yoga sequence to their exercise routine that has been shown to build bone. It’ll give their bones and muscles the boost they need.

Editor’s Note: Dr. Fishman is recruiting participants for a study on the effects of yoga and botulinum toxin on adolescent idiopathic scoliosis (AIS). See details.

1. Dr. James Paintin, Professor Cyrus Cooper, and Professor Elaine Dennison, "Osteosarcopenia" Br J Hosp Med (Lond). 2018 May 2; 79(5): 253–258. doi: 10.12968/hmed.2018.79.5.253
2. Ben Kirk, Jesse Zanker, and Gustavo Duque, "Osteosarcopenia: epidemiology, diagnosis, and treatment—facts and numbers" J Cachexia Sarcopenia Muscle. 2020 Jun; 11(3): 609–618. Published online 2020 Mar 22. doi: 10.1002/jcsm.12567
3. Yan-Jiao Wang, Yi Wang, Jun-Kun Zhan, Zhi-Yong Tang, Jie-Yu He, Pan Tan, Hui-Qian Deng, Wu Huang, You-Shuo Liu, "Sarco-Osteoporosis: Prevalence and Association with Frailty in Chinese Community-Dwelling Older Adults" Int J Endocrinol. 2015;2015:482940. doi: 10.1155/2015/482940. Epub 2015 Jul 27.
4. Ebrahim Bani Hassan, Gustavo Duque, "Osteosarcopenia: A new geriatric syndrome" The Royal Australian College of General Practitioners 2017
5. Cariati I, Bonanni R, Onorato F, Mastrogregori A, Rossi D, Iundusi R, Gasbarra E, Tancredi V, Tarantino U. Role of Physical Activity in Bone–Muscle Crosstalk: Biological Aspects and Clinical Implications. Journal of Functional Morphology and Kinesiology. 2021; 6(2):55. https://doi.org/10.3390/jfmk6020055.
6. Ye, H. Mechanic stress generated by a time-varying electromagnetic field on bone surface. Med. Biol. Eng. Comput. 2018, 56, 1793–1805. [Google Scholar] [CrossRef]
7. Ahn, N.; Kim, K. Effects of 12-week exercise training on osteocalcin, high-sensitivity C-reactive protein concentrations, and insulin resistance in elderly females with osteoporosis. J. Phys. Ther. Sci. 2016, 28, 2227–2231. [Google Scholar] [CrossRef]
8. Kim, Y.-S.; Nam, J.S.; Yeo, D.-W.; Kim, K.R.; Suh, S.-H.; Ahn, C.W. The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males. Clin. Endocrinol. 2015, 82, 686–694. [Google Scholar] [CrossRef] [PubMed]
9. Mera, P.; Laue, K.; Ferron, M.; Confavreux, C.; Wei, J.; Galán-Díez, M.; Lacampagne, A.; Mitchell, S.J.; Mattison, J.A.; Chen, Y.; et al. Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell Metab. 2016, 23, 1078–1092. [Google Scholar] [CrossRef] [PubMed]
10. Lin, X.; Hanson, E.; Betik, A.C.; Brennan-Speranza, T.C.; Hayes, A.; Levinger, I. Hindlimb Immobilization, But Not Castration, Induces Reduction of Undercarboxylated Osteocalcin Associated With Muscle Atrophy in Rats. J. Bone Miner. Res. 2016, 31, 1967–1978. [Google Scholar] [CrossRef]
11. Mera, P.; Laue, K.; Wei, J.; Berger, J.M.; Karsenty, G. Osteocalcin is necessary and sufficient to maintain muscle mass in older mice. Mol. Metab. 2016, 5, 1042–1047.
12. Ducy, P. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia 54, 1291 (2011). https://doi.org/10.1007/s00125-011-2155-z
13. Lu YH, Rosner B, Chang G, Fishman LM. Twelve-Minute Daily Yoga Regimen Reverses Osteoporotic Bone Loss. Top Geriatr Rehabil. 2016;32(2):81-87. doi:10.1097/TGR.0000000000000085
14. Hiroshi Kaji, "Interaction between Muscle and Bone" J Bone Metab. 2014 Feb;21(1):29-40. doi: 10.11005/jbm.2014.21.1.29. Epub 2014 Feb 28.
15. E. Michael Lewiecki, "Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases" Ther Adv Musculoskelet Dis. 2014 Apr; 6(2): 48–57. doi: 10.1177/1759720X13510479
16. W Kemmler 1, L Häberle, S von Stengel, "Effects of exercise on fracture reduction in older adults: a systematic review and meta-analysis" Osteoporos Int. 2013 Jul;24(7):1937-50. doi: 10.1007/s00198-012-2248-7. Epub 2013 Jan 10.
17. Raimunda B Silva 1, Guy D Eslick, Gustavo Duque, "Exercise for falls and fracture prevention in long term care facilities: a systematic review and meta-analysis" J Am Med Dir Assoc. 2013 Sep;14(9):685-9.e2. doi: 10.1016/j.jamda.2013.05.015. Epub 2013 Jul 13.
18. Francesca Remelli, Aurora Vitali, Amedeo Zurlo, and Stefano Volpato, "Vitamin D Deficiency and Sarcopenia in Older Persons" Nutrients. 2019 Dec; 11(12): 2861. Published online 2019 Nov 21. doi: 10.3390/nu11122861 
19. Paul Lips, Natasja M van Schoor, "The effect of vitamin D on bone and osteoporosis" Best Pract Res Clin Endocrinol Metab. 2011 Aug;25(4):585-91. doi: 10.1016/j.beem.2011.05.002.
20. A Oliveira, C Vaz, "The role of sarcopenia in the risk of osteoporotic hip fracture" Clin Rheumatol. 2015 Oct;34(10):1673-80. doi: 10.1007/s10067-015-2943-9. Epub 2015 Apr 26.
21. J Compston, A Cooper, C Cooper, et al., "UK clinical guideline for the prevention and treatment of osteoporosis" Arch Osteoporos. 2017 Dec;12(1):43. doi: 10.1007/s11657-017-0324-5. Epub 2017 Apr 19.
22. Robert P. Heaney, M.D., "Calcium: The Real Story" http://blogs.creighton.edu/heaney/2013/01/04/calcium-the-real-story 
23. https://www.nap.edu/read/10490/chapter/12 
24. Xiong JP, Stehle T, Diefenbach B, et. al. (October 2001). "Crystal structure of the extracellular segment of integrin alpha Vbeta3". Science. 294 (5541): 339–45. PMID 11546839.
25. Shan, C., Ghosh, A., Guo, Xz. et al. Roles for osteocalcin in brain signalling: implications in cognition- and motor-related disorders. Mol Brain 12, 23 (2019). https://doi.org/10.1186/s13041-019-0444-5
26. Moser SC, van der Eerden BCJ. Osteocalcin-A Versatile Bone-Derived Hormone. Front Endocrinol (Lausanne). 2019 Jan 10;9:794. doi: 10.3389/fendo.2018.00794. PMID: 30687236
27.