insights

Read Time: 4 Minutes

Supporting bone-related hormonal balance is essential for optimal bone and overall health. In addition to aging, menopause, male hypogonadism, and some medications, a range of chronic diseases may also contribute to osteoporosis or reduced bone quality, including inflammatory bowel disease,¹ liver and kidney diseases,^2,3 celiac disease,^4,5 and diabetes.⁶ The functional medicine model approaches bone health by considering the multiple influential factors. This includes addressing potential bone-related hormone dysfunction.

Hormones operate within a web of interconnection impacted by many factors, with the balance ultimately affecting the function and health of body systems. The skeletal system is no exception, as multiple hormones modulate and support bone health. This complex network of regulatory hormones responds to changes in blood calcium and phosphorous levels and affects the formation and turnover of bone throughout the life stages. What modifiable lifestyle factors and other foundational functional medicine approaches support the skeletal system and bone-related hormones?

Bone Hormones: A Complex Web

Regulatory hormones play a critical role in the lifelong bone remodeling process. The following are some of those hormones, with a brief description of their complex roles in supplying necessary minerals for bone development, monitoring mineral blood levels, and maintaining or influencing bone homeostasis:

• Parathyroid hormone (PTH): This calcium-regulating hormone controls the level of calcium in the blood and stimulates both resorption and formation of bone.⁷
• Calcitriol (1,25 dihydroxy vitamin D): Also a noted calcium-regulating hormone, calcitriol is produced from vitamin D and is required for calcium absorption.⁷
• Calcitonin: A third calcium-regulating hormone, calcitonin protects against excessive blood calcium levels during early childhood by inhibiting bone turnover and decreasing reabsorption; however, its role in adult calcium homeostasis is unclear.⁷
• Sex hormones: Estrogen is a key regulator of bone remodeling in women and men and acts on both osteoclasts and osteoblasts. Testosterone is important for skeletal growth and is also a source of estrogen in the body.^7,8
• Growth hormones: Growth hormone and its production of the insulin-like growth factor (IGF-1) influences bone formation.⁷
• Thyroid hormones: These hormones are required for skeletal maturation and influence adult bone maintenance.^7,9
• Cortisol: Large amounts of this adrenal gland hormone block bone growth. Glucocorticoid-induced osteoporosis is the most common secondary cause of osteoporosis.^7,10
• Insulin: Important for bone growth, insulin signaling regulates both bone formation and bone resorption.^7,11
• Leptin: This circulating hormone has direct and indirect influences on bone metabolism that research continues to elucidate.^7,12

Bone Hormones: Lifestyle-Based Support

A foundational principle for the assessment and treatment of all hormonal imbalances is IFM’s “PTSD” mnemonic, which identifies points of leverage where personalized interventions help to restore hormonal balance through the improvement of production, transport, sensitivity, and detoxification of hormones. These tailored treatments may include a range of lifestyle-based approaches. Recent studies continue to indicate that anti-inflammatory Mediterranean-style diets,^13,14 weight-bearing and resistance-based exercise,^15,16 and stress management^17-19 help to support bone health overall. In addition to a nutrient-dense diet, specific vitamins and minerals, supplements, and nutraceuticals help to positively impact bone density and quality. Calcium, vitamin D, vitamin K, isoflavones (abundant in soybeans and other legumes), omega-3 fatty acids, and probiotics are several examples.^20-25

Specific to supporting those hormones that regulate bone homeostasis, nutrition and other modifiable lifestyle factors also play a critical role. Recent research studies provide a sample of examples:

• A recent meta-analysis of 42 studies found that mindfulness-based stress reduction interventions that included yoga asanas were associated with improved regulation of both the sympathetic nervous system and the hypothalamic-pituitary-adrenal system. Specifically, reduced evening cortisol and waking cortisol levels were noted.²⁶
• A 2019 randomized controlled trial (RCT) (n=626 overweight/obese adults with metabolic syndrome) reported that compared to controls, those participants receiving the 12-month intervention (energy-restricted Mediterranean diet, physical activity promotion, and behavioral support) had reduced circulating levels of leptin and significantly improved insulin sensitivity.²⁷
• Compelling results from a 2020 animal study suggested that the short-chain fatty acid butyrate was required for PTH to stimulate bone formation and increase bone mass.²⁸ This study highlights the developing research on the relationship between maintaining a healthy gut microbiome and optimizing bone health.^29,30 

Conclusion

A team of hormones regulates bone metabolism and works to maintain bone homeostasis. Lifestyle-based interventions from nutrition to stress management help to support their function and maintain skeletal integrity. At IFM’s Hormone Advanced Practice Module (APM), learn from functional medicine experts about how the complex interplay of hormones impacts bone health and how you can use IFM tools to determine the most appropriate treatments for your patients.

Related Articles

The Bone and Mitochondria Connection

Bone Health Risks With High-Dose Topical Corticosteroids

Menopause Hormone Therapy

References

1. Kärnsund S, Lo B, Bendtsen F, Holm J, Burisch J. Systematic review of the prevalence and development of osteoporosis or low bone mineral density and its risk factors in patients with inflammatory bowel disease. World J Gastroenterol. 2020;26(35):5362-5374. doi:10.3748/wjg.v26.i35.5362
2. Jeong HM, Kim DJ. Bone diseases in patients with chronic liver disease. Int J Mol Sci. 2019;20(17):4270. doi:10.3390/ijms20174270
3. Carrillo-López N, Martínez-Arias L, Fernández-Villabrille S, et al. Role of the RANK/RANKL/OPG and Wnt/β-catenin systems in CKD bone and cardiovascular disorders. Calcif Tissue Int. 2021;108(4):439-451. doi:10.1007/s00223-020-00803-2
4. Fedewa MV, Bentley JL, Higgins S, Kindler JM, Esco MR, MacDonald HV. Celiac disease and bone health in children and adolescents: a systematic review and meta-analysis. J Clin Densitom. 2020;23(2):200-211. doi:10.1016/j.jocd.2019.02.003
5. Ganji R, Moghbeli M, Sadeghi R, Bayat G, Ganji A. Prevalence of osteoporosis and osteopenia in men and premenopausal women with celiac disease: a systematic review. Nutr J. 2019;18(1):9. doi:10.1186/s12937-019-0434-6
6. Thong EP, Milat F, Enticott JC, et al. The diabetes-fracture association in women with type 1 and type 2 diabetes is partially mediated by falls: a 15-year longitudinal study. Osteoporos Int. 2021;32(6):1175-1184. doi:10.1007/s00198-020-05771-9
7. Office of the Surgeon General (US). The basics of bone in health and disease. In: Office of the Surgeon General (US). Bone Health and Osteoporosis: A Report of the Surgeon General. Office of the Surgeon General (US); 2004:Chapter 2. https://www.ncbi.nlm.nih.gov/books/NBK45504/
8. Emmanuelle NE, Marie-Cécile V, Florence T, et al. Critical role of estrogens on bone homeostasis in both male and female: from physiology to medical implications. Int J Mol Sci. 2021;22(4):1568. doi:10.3390/ijms22041568
9. Bassett JH, Williams GR. Role of thyroid hormones in skeletal development and bone maintenance. Endocr Rev. 2016;37(2):135-187. doi:10.1210/er.2015-1106
10.  Compston J. Glucocorticoid-induced osteoporosis: an update. Endocrine. 2018;61(1):7-16. doi:10.1007/s12020-018-1588-2
11.  Conte C, Epstein S, Napoli N. Insulin resistance and bone: a biological partnership. Acta Diabetol. 2018;55(4):305-314. doi:10.1007/s00592-018-1101-7
12.  Upadhyay J, Farr OM, Mantzoros CS. The role of leptin in regulating bone metabolism. Metabolism. 2015;64(1):105-113. doi:10.1016/j.metabol.2014.10.021
13.  Boushey C, Ard J, Bazzano L, et al. Dietary Patterns and Bone Health: A Systematic Review. USDA Nutrition Evidence Systematic Review; July 2020. doi:10.52570/NESR.DGAC2020.SR0105
14.  Malmir H, Saneei P, Larijani B, Esmaillzadeh A. Adherence to Mediterranean diet in relation to bone mineral density and risk of fracture: a systematic review and meta-analysis of observational studies. Eur J Nutr. 2018;57(6):2147-2160. doi:10.1007/s00394-017-1490-3
15.  Watson SL, Weeks BK, Weis LJ, Harding AT, Horan SA, Beck BR. High-intensity resistance and impact training improves bone mineral density and physical function in postmenopausal women with osteopenia and osteoporosis: the LIFTMOR randomized controlled trial [published correction appears in J Bone Miner Res. 2019;34(3):572]. J Bone Miner Res. 2018;33(2):211-220. doi:10.1002/jbmr.3284
16.  LeBoff MS, Greenspan SL, Insogna KL, et al. The clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. Published online April 28, 2022. doi:10.1007/s00198-021-05900-y
17.  Ng JS, Chin KY. Potential mechanisms linking psychological stress to bone health. Int J Med Sci. 2021;18(3):604-614. doi:10.7150/ijms.50680
18.  Wippert PM, Rector M, Kuhn G, Wuertz-Kozak K. Stress and alterations in bones: an interdisciplinary perspective. Front Endocrinol (Lausanne). 2017;8:96. doi:10.3389/fendo.2017.00096
19.  Turner AI, Smyth N, Hall SJ, et al. Psychological stress reactivity and future health and disease outcomes: a systematic review of prospective evidence. Psychoneuroendocrinology. 2020;114:104599. doi:10.1016/j.psyneuen.2020.104599
20.  Bone Health and Osteoporosis Foundation. Nutrients: bone healthy ingredients. Accessed May 09, 2022. https://www.bonehealthandosteoporosis.org/preventing-fractures/nutrition-for-bone-health/nutrients/
21.  Chen LR, Ko NY, Chen KH. Isoflavone supplements for menopausal women: a systematic review. Nutrients. 2019;11(11):2649. doi:10.3390/nu11112649
22.  Shen D, Zhang X, Li Z, Bai H, Chen L. Effects of omega-3 fatty acids on bone turnover markers in postmenopausal women: systematic review and meta-analysis. Climacteric. 2017;20(6):522-527. doi:10.1080/13697137.2017.1384952
23.  Lambert MNT, Thybo CB, Lykkeboe S, et al. Combined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women: a randomized controlled trial. Am J Clin Nutr. 2017;106(3):909-920. doi:10.3945/ajcn.117.153353
24.  Nilsson AG, Sundh D, Backhed F, Lorentzon M. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018;284(3):307-317. doi:10.1111/joim.12805
25.  Slupski W, Jawien P, Nowak B. Botanicals in postmenopausal osteoporosis. Nutrients. 2021;13(5):1609. doi:10.3390/nu13051609
26.  Pascoe MC, Thompson DR, Ski CF. Yoga, mindfulness-based stress reduction and stress-related physiological measures: a meta-analysis. Psychoneuroendocrinology. 2017;86:152-168. doi:10.1016/j.psyneuen.2017.08.008
27.  Salas-Salvadó J, Díaz-López A, Ruiz-Canela M, et al. Effect of a lifestyle intervention program with energy-restricted Mediterranean diet and exercise on weight loss and cardiovascular risk factors: one-year results of the PREDIMED-Plus trial. Diabetes Care. 2019;42(5):777-788. doi:10.2337/dc18-0836
28.  Li JY, Yu M, Pal S, et al. Parathyroid hormone-dependent bone formation requires butyrate production by intestinal microbiota. J Clin Invest. 2020;130(4):1767-1781. doi:10.1172/JCI133473
29.  Ding K, Hua F, Ding W. Gut microbiome and osteoporosis. Aging Dis. 2020;11(2):438-447. doi:10.14336/AD.2019.0523
30.  Lucas S, Omata Y, Hofmann J, et al. Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun. 2018;9(1):55. doi:10.1038/s41467-017-02490-4