Optimal DX Supplement Series: Bone Health

Bone is a metabolically active, dynamic organ that continually renews itself throughout life. This process, known as bone remodeling, involves osteoclast breakdown of old bone, followed by osteoblast creation of new bone.

Bone remodeling occurs in three main stages: resorption, wherein osteoclasts remove old bone; reversal, wherein cells prepare the bone surface for new growth; and formation, wherein osteoblasts build new bone (Hadjidakis 2006).

Ideally, resorption and formation are in homeostatic balance so that old bone is continuously replaced by new tissue. Many factors, including hormones (especially estrogen), growth factors, and cytokines, help regulate the bone-remodeling process systemically and locally (Hadjidakis 2006).

Bone loss can result from not reaching peak bone mass in youth, excessive bone loss after reaching peak mass, or a diminished ability to form new bone during remodeling (Raisz 1999). Dietary and lifestyle factors that may contribute to bone loss include vitamin and mineral deficiencies, a lack of physical activity, especially weight-bearing exercises, certain prescription medications, smoking, heavy alcohol use, and an unhealthy body weight (Office of the Surgeon General 2024).

Supportive Supplements

Vitamin K2

1.5 mg/d (maintenance) to 45 mg/d (Iwamoto 1999, Knapen 2007, Koitaya 2014)

• Supplementation of 45 mg/d of vitamin K2 for one year suppressed a decrease in spinal bone mineral density as compared with no treatment (Iwamoto 1999).
• Supplementation of 45 mg/d of vitamin K2 for three years in postmenopausal women increased bone mineral circumference, which is protective against fractures and falls (Knapen 2007).
• Postmenopausal women taking 1.5 mg/d of vitamin K for three years had no change in their forearm bone mineral density, whereas the placebo group experienced a decrease (Koitaya 2014).

Vitamin D

500 IU/d to 5,000 IU/d (Bislev 2019, Meier 2004)

• 2,800 IU/d of vitamin D3 for three months in healthy postmenopausal women with low 25(OH)D, i.e., below 20 ng/mL (50 nmol/L) and high parathyroid hormone levels, i.e., above 65 pg/mL (6.9 pmol/L), experienced significantly increased vitamin D levels, decreased parathyroid hormone (PTH), improved bone strength and trabecular thickness in the tibia, and improved volumetric bone mineral density in the trochanter and femoral neck (Bislev 2019).
• Healthy adults taking 500 IU/d of vitamin D3 and 500 mg/day of calcium during the winter months (October–April) prevented seasonal changes in bone turnover and bone loss in healthy adults (Meier 2004).
• A systematic review and meta-analysis found that vitamin D3 supplementation improved bone mineral density at the hip, lumbar spine, and femoral neck (Kazemian 2023).

Calcium

Calcium from food sources is best; however, if dietary calcium intake is insufficient, then supplementation may be indicated.

RDAs:

• 19–50 years old: 1,000 mg per day for both men and women
• 51–70 years old: 1,000 mg per day for men and 1,200 mg per day for women. Over 70 years old: 1,200 mg per day for both men and women.

With calcium supplementation, patients should be monitored for cardiovascular risk factors.

• A meta-analysis of six RCTs using combined supplementation with 400-800 IU/d of vitamin D and 1,000-1,200 mg/d calcium found a 6% reduced risk of any fracture and a 16% reduced risk of hip fracture (Yao 2019).
• A meta-analysis of 29 randomized trials found that calcium, or calcium combined with vitamin D, can reduce the risk of fractures and slow bone loss in people aged 50 and older. Higher doses of calcium (1,200 mg or more) and vitamin D (800 IU or more) were more effective (Tang 2007).

Magnesium

250 mg to 350 mg twice daily in divided doses (Stengler 2016)

• Supplementation with 1,830 mg/day of magnesium citrate for 30 days in postmenopausal women suppressed bone turnover, as indicated by significantly improved hormonal and other markers of bone turnover (Aydin 2010).
• A systematic review with meta-analysis showed that lower serum Mg concentrations were associated with a significantly higher risk of incident fractures (Dominguez 2023).
• Another systematic review and meta-analysis indicated that a higher magnesium intake from food and/or supplements may support an increase in hip and femoral neck bone mineral density (Groenendijk 2022).

References

Aydın, Hasan, et al. "Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women." Biological trace element research 133 (2010): 136-143.

Bislev, Lise Sofie, et al. "Bone microstructure in response to vitamin D3 supplementation: a randomized placebo-controlled trial." Calcified tissue international 104.2 (2019): 160-170.

Dominguez, Ligia J., et al. "Association between serum magnesium and fractures: a systematic review and meta-analysis of observational studies." Nutrients 15.6 (2023): 1304.

Groenendijk, Inge, et al. "Impact of magnesium on bone health in older adults: A systematic review and meta-analysis." Bone 154 (2022): 116233.

Hadjidakis, Dimitrios J., and Ioannis I. Androulakis. "Bone remodeling." Annals of the New York academy of sciences 1092.1 (2006): 385-396.

Iwamoto I, Kosha S, Noguchi S, et al. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Maturitas. 1999;31(2):161-164. doi:10.1016/s0378-5122(98)00114-5

Kazemian, Elham et al. “Effect of supplemental vitamin D3 on bone mineral density: a systematic review and meta-analysis.” Nutrition reviews vol. 81,5 (2023): 511-530. doi:10.1093/nutrit/nuac068

Knapen MH, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007;18(7):963-972. doi:10.1007/s00198-007-0337-9

Koitaya N, Sekiguchi M, Tousen Y, et al. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Miner Metab. 2014;32(2):142-150. doi:10.1007/s00774-013-0472-7

Meier, Christian, et al. "Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open‐label prospective trial." Journal of Bone and Mineral Research 19.8 (2004): 1221-1230.

Office of the Surgeon General (US). Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville (MD): Office of the Surgeon General (US); 2004. 6, Determinants of Bone Health. Accessed August 13, 2024. https://www.ncbi.nlm.nih.gov/books/NBK45503/

Raisz, Lawrence G. "Physiology and pathophysiology of bone remodeling." Clinical chemistry 45.8 (1999): 1353-1358.

Stengler M, et al. Prescription for Natural Cures: A Self-care Guide for Treating Health Problems With Natural Remedies Including Diet, Nutrition, Supplements, and Other Holistic Methods. Third ed. Turner Publishing Co, 2016.

Tang, Benjamin MP, et al. "Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis." The lancet 370.9588 (2007): 657-666.

Yao, Pang, et al. "Vitamin D and calcium for the prevention of fracture: a systematic review and meta-analysis." JAMA network open 2.12 (2019): e1917789-e1917789.