Vitamin D and Bone Health

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Vitamin D and Bone Health

Introduction

Vitamin D plays a vital role in the maintenance of healthy mineralized skeleton for vertebrates including human beings. Sunlight is normally behind the vitamin D3 photo-production in the skin. After its formation, vitamin D3 is sequentially metabolized in the kidney and liver to 1,25-dihydroxyvitamin D.1 The main function of the latter is keeping the concentration of serum calcium and phosphorus within a normal range to ensure the maintenance of vital cellular functions and the promotion of skeletal mineralization. Many foods lack vitamin D and those that are fortified with vitamin D contain variable amounts and humans cannot rely on them as he only source of vitamin D. Sunlight exposure provides humans and animals with the required Vitamin D. Deficiency and insufficiency of vitamin D has been recognized as the main cause of bone diseases among children and the elderly. The deficiency of vitamin D causes osteomalacia and exacerbates osteoporosis.1 Generally, studies conclude that an increased intake of calcium to 1000-1500 mg/d alongside a sufficient of vitamin D of not less than 400 IU/d is essential for the maintenance of good bone health. This paper will discuss the biochemical mechanism of vitamin D for bone health and the summary of published scientific evidence of the same.

Potential Mechanisms

Vitamin D plays the role of regulating the levels of blood calcium by enhancing calcium intestinal absorption and mitigating its elimination. In addition, it deposits calcium in the bone and removes it from bone in order to meet the needs of the body.2 The deficiency of vitamin D leads to a decreased calcium absorption and elevated parathyroid hormone (PTH) concentration. PTH is a hormone which increases the levels of calcium by releasing calcium from the bones. In the long run, the deficiency of vitamin D results in a bone mass loss that weakens the bone and leads to osteoporosis.1 Adequate intake of vitamin D leads to a decrease of bone loss be mitigating PTH secretion and prevents the excessive remodeling of bones (bone turnover).

Humans attain peak bone mass in their thirties with physical activities, genetics, lifestyle, and nutrition factors playing a major role in accumulating and maintaining their bones. Bone loss related to age is experienced when one is their forties leading to a slow decline of bone mineral density (BMD) although this process is augmented among females in their menopause owing to the likelihood of oestrogen deficiency causing bone loss.3 The bone disease development in later stages of life relates to humans attaining maximum peak bone mass and maintaining bone mass during adulthood. Studies show that insufficient intake of vitamin D over a long period of time results in demineralization of bones. Furthermore, the deficiency of vitamin D results in a decrease in the absorption of calcium and eventually the release of calcium from bone to maintain the concentration of calcium.3 A continuous turnover of bones and reabsorption tends to weaken the bone architecture and increases the risk of fractures through secondary hyperparathyroidism eventually resulting in osteoporosis and osteomalacia.

There exists a direct relation between bone mineral density (BMD) and risk of fracture with a decreased bone density and strength related to a high incidence fracture rate. Usually, fractures tend to take place on the spine, hip, and wrist. Fractures carry significant costs of health and leads to increase in mortality and decrease in life quality. Incidences of fractures increase with age; thus it is imperative for humans to establish preventive strategies so as to mitigate the development of such conditions.4 Given the relationship that exists between bone mineralization and vitamin D, optimal status of vitamin D is vital to minimize risk of fractures.

At any time, the vitamin D actions rely on both the status of vitamin D and dietary intake of calcium. When there is inadequate intake of dietary calcium and the status of vitamin D is deficient, it is demonstrated that there would be a development of osteomalacic bone with an increased lag time of mineralization.1 Under such conditions, there is an activation of phosphate homeostatic and plasma calcium mechanisms that include the system of endocrine vitamin D through plasma 1,25-dihydroxyvitamin D. The concentration of PTH can increase which elevates the CYP27B1 enzyme activity within the kidney to allow for 1,25-dihydroxyvitamin D concentrations although the concentrations of serum 25-hydroxyvitamin D might fall below 40 nmol/L.2 Under such conditions, there is a maintenance of intestinal phosphate and calcium absorption and there is a stimulation of osteoclastogenesis through 1,25-dihydroxyvitamin D and PTH interaction acting on osteoblasts to increase the reabsorption of bones. Moreover, there is the augmentation of bone cell activity which increases the number of osteoblasts multiplication and thus enhancing the RANKL expression to stimulate further osteoclastogenesis.2 When the concentrations of serum 25-hydroxyvitamin D is below 20 nmol/L, there is inadequate substrate for the renal CYP27B1 enzyme and the concentration of 1,25-dihydroxyvitamin D fall resulting in the fall of intestinal calcium absorption and osteomalacia and hypocalcemia development.

When there is a sufficient intake of dietary calcium but the status of vitamin D is low and vice versa, phosphate homeostasis and plasma calcium is maintained. Based on the serum 25-hydroxyvitamin D or dietary calcium concentration, the plasma calcium homeostatic mechanism may mitigate the concentrations of 1,25-dihydroxyvitamin D and serum PTH.2 But the RANKL expression in bone tissues is elevated with an increase in osteoclast surface and bone volumes and reabsorption are decreased. Mineralization lag times are then stabilized and the histology of bones demonstrates osteoporosis.

Summary of published scientific evidence to date

A study conducted by Veldurthy5 indicates that there are two actions that vitamin D exerts in order to modify bone health. Its findings show how vitamin D maintains phosphate homeostasis and plasma calcium preventing osteomalacia development. The authors states that the plasma 1,25-dihydroxyvitamin D contributes to the maintenance of plasma calcium homeostasis via an osteoblasts action in order to stimulate bone resorption and osteoclastogenesis enhancing the phosphate and calcium flow into the compartment of plasma.5 In addition, the authors assert that the serum 25-hydroxyvitamin D concertation is critical in order to ensure that sufficient of 1,25-dihydroxyvitamin D plasma concentrations is maintained and the absorption of intestinal calcium is 20 nmol/L. The other action by vitamin D is that it maintains the volume of mineralized bone tissue as assessed by the density of bone mineral and cortical and trabecular bone volumes. Therefore, it leads to the prevention osteoporosis development and reduction of risks of fracture.1 In this case, bone mineral density, bone histology, and increased risk of fracture, are all related to the concentration of serum 25-hydroxyvitamin D as opposed to serum 1,25-dihydroxyvitamin D.5 Dietary calcium intake and vitamin D interaction is possible since the most consistent data from randomized controlled trials for reduction of risk of fractures has been demonstrated when such nutrients combine.

Another review by Park et al. came to a conclusion that the greatest contributors to fractures are falls but the study also reports that the deficiency of vitamin D associates with weakness of the muscles and an increase in pre-disposition for falling.6 Such an association is not surprising given that this study shows that the expression of the VDR occurs in both myoblast cells and skeletal muscles. Evidence of the study demonstrates that vitamin D increases cellular growth and protein synthesis in muscle cells with increased number and size of type 2 muscle fibers which are vital as they are the first muscle fibers that are recruited when one falls.2 6 In support of this, an observational study by Burt et al. report that the plasma concentration of vitamin D in the 40-90nmol/L range is associated with more enhanced musculoskeletal function relative to serum concentrations <40nmol/L.6 7 In addition, the findings of the study suggest that reduced muscular functions in vitamin D deficient subjects could be available prior to the recognition of bone disease indications.7 8 Clearly, this evidence has provided a mechanism to support muscle strength improvement and in defacto bone health if vitamin D is supplemented.

Conclusion

Evidently, vitamin D is vital for bone health because inadequate intakes leads to diseases such as osteomalacia and enhanced fracture risk and increased bone metabolism. Research findings’ evidence to-date tends to indicate that vitamin D supplementation among those who are at a higher risk of impaired bone health has a favorable impact on the prevention of fractures. Many studies have shown that vitamin D improves BMD and enhances the function of the muscles as well resulting in a decrease in the number of falls. Vitamin D also can modulate the impact of pro-inflammatory cytokines on metabolism of bones. However, the required supplementation level is still under debate since various studies indicate different regiments of dosage. Many meta-analyses and trial have indicated that an 800 IU/d dose of vitamin D combined with adequate calcium intake is optimal. However, other studies have suggested greater benefits at higher intakes. There is a need for further studies to verify the optimum vitamin D dosage for better outcome.

References

1. Falchetti, A., Rossi, E., Cosso, R., Buffa, A., Corvaglia, S., & Malavolta, N. (2016). Vitamin D and Bone Health. Food and Nutrition Sciences, 7(11), 1033-1051.

2. Khammissa, R. A. G., Fourie, J., Motswaledi, M. H., Ballyram, R., Lemmer, J., & Feller, L. (2018). The biological activities of vitamin D and its receptor in relation to calcium and bone homeostasis, cancer, immune and cardiovascular systems, skin biology, and oral health. BioMed research international, 2018.

3. Hill, T. R., & Aspray, T. J. (2017). The role of vitamin D in maintaining bone health in older people. Therapeutic advances in musculoskeletal disease, 9(4), 89-95.

4. Dzik, K. P., & Kaczor, J. J. (2019). Mechanisms of vitamin D on skeletal muscle function: oxidative stress, energy metabolism and anabolic state. European journal of applied physiology, 119(4), 825-839.

5. Veldurthy, V., Wei, R., Oz, L., Dhawan, P., Jeon, Y. H., & Christakos, S. (2016). Vitamin D, calcium homeostasis and aging. Bone research, 4(1), 1-7.

6. Park, J. E., Pichiah, P. T., & Cha, Y. S. (2018). Vitamin D and metabolic diseases: growing roles of vitamin D. Journal of obesity & metabolic syndrome, 27(4), 223.

7. Burt, L. A., Billington, E. O., Rose, M. S., Raymond, D. A., Hanley, D. A., & Boyd, S. K. (2019). Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength: a randomized clinical trial. Jama, 322(8), 736-745.

8. Fischer, V., Haffner-Luntzer, M., Amling, M., & Ignatius, A. (2018). Calcium and vitamin D in bone fracture healing and post-traumatic bone turnover. Eur Cell Mater, 35, 365-385.