Vitamin D and Osteoporosis

Take-home points

• Osteoporosis is a health condition that weakens bones, reduces quality of life, and increases the risk of an early death.
• Correcting a vitamin D deficiency is likely to improve bone mineral density and reduce the risk of osteoporosis and associated falls.
• Maintaining a normal testosterone level may improve the effectiveness of vitamin D supplementation, but more evidence is needed.

‍What is vitamin D and osteoporosis?

Vitamin D is a hormone that helps to control the amount of calcium and phosphate in the blood. Unlike most nutrients, vitamin D is mostly synthesised in skin cells when exposed to UV radiation from sun exposure. Food is also a source of vitamin D but not a particularly good one—if reliant on food alone, you risk vitamin D deficiency.  

Along with its important role in immunity, you might hear that vitamin D helps to “maintain healthy bones”.  That is true: the active form of vitamin D is needed to absorb dietary calcium from the small intestine and aid its uptake into bone. It is for this reason that vitamin D is closely linked to preventing and treating osteoporosis—a worldwide disease characterised by low bone mineral density and mass that leaves you prone to bone fractures, even from low impact.  

What is a normal level of vitamin D?

There is some debate about what defines a normal level of vitamin D. According to a recent statement from The Journal of Bone Metabolism¹ and clinical summaries from the National Institute for Health and Care Excellence², sufficient vitamin D is when the 25(OH)D measurement (a form of vitamin D in blood) is equal to or more than 20 ng/mL (50 nmol/ L). Vitamin D insufficiency or deficiency is when 25(OH)D is below 20 ng/mL (50 nmol/ L).

Does vitamin D prevent or treat osteoporosis?

The research on vitamin D and osteoporosis (or markers of bone health) is mixed. On the one hand, since most people are not vitamin D deficient, it is unlikely that the average person will benefit from further increasing their vitamin D levels. A large analysis of 81 high-quality studies found reliable evidence that plain vitamin D supplementation does not reduce hip fractures, for example.³ Other studies that had older adults supplement vitamin D for multiple years similarly found that, despite increasing the amount of vitamin D in the blood, there was no clear improvement in bone mineral density.^4,5

However, as is the case for all nutrients, vitamin D works within ranges. Both low (“deficiency”) and high (“toxicity”) levels typically lead to poor health outcomes, while in between there is a healthy range of vitamin D that everyone should aim to achieve. Therefore, if someone is already within the ‘healthy range’ to start with, there is no scope for additional benefit. The potential benefit of vitamin D applies only to those who achieve healthy levels from a state of deficiency or toxicity.

Vitamin D supplementation in clinically deficient patients does not necessarily improve osteoporosis endpoints,⁶ but the bulk of evidence suggests that it does. For instance, in secondary analyses of a couple of trials that did not report benefit or vitamin D supplementation, benefits to bone mineral density were noted in the select group of participants who corrected their vitamin D (<30 ng/mL) via supplementation.⁷ Another large analysis of well-controlled trials also reported the possibility that vitamin D supplementation of 800 IU/day (20 μg/day) improves bone mineral density in older adults who have serum 25(OH)D less than 20 ng/mL.⁸

Do testosterone levels influence the efficacy of vitamin D in patients with osteoporosis?

Researchers have suggested that maintaining optimal testosterone levels is essential in preventing osteoporosis and its complications in elderly men.⁹ Converging evidence suggests that testosterone replacement therapy (TRT) could maintain or improve bone mineral density among hypogonadal men.^10,11

Interestingly, some evidence also suggests that vitamin D supplementation is more likely to benefit a patient with osteoporosis if they have higher testosterone levels. This is by no means conclusive but it is plausible. Some scientists have proposed that testosterone is involved in the biological response to vitamin D in the classical organs,¹² such as intestine and bone, and this observation may partly explain the pathogenesis of osteoporosis in hypogonadal men.¹³

In one study of 199 older men and 246 women (65 years old and above), participants were assessed for their risk of falls in the 3 years after a hormone assessment.¹⁴ The results were that higher testosterone levels predicted more than a 60% lower risk of falling in both genders. In those with the highest testosterone levels who also supplemented with vitamin D and calcium, the fall reduction was enhanced by a further 6-19%. And when compared to adults with the lowest testosterone levels, those with the highest testosterone levels who also supplemented vitamin D and calcium had approximately 85% less falls.  

More evidence is needed to explore whether the relationship between vitamin D and osteoporosis is mediated by testosterone levels. If this is indeed the case, it will add weight to the position that all patients with (or at risk of) osteoporosis should be treated for deficiencies in vitamin D and testosterone.

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References

1. Han A et al. J Bone Metab. 2022;29(4): 205–215.

2. https://cks.nice.org.uk/topics/vitamin-d-deficiency-in-adults/

3. Bolland MJ et al. Lancet Diabetes Endocrinol. 2018;6(11):847-858.

4. Burt LA et al. JAMA. 2019; 322(8): 736–745.

5. Leboff MF. J Bone Miner Res. 2020; 35(5): 883–893.

6. Isaks GJ. BMC Musculoskelet Disord; 2007; 8: 26.

7. Macdonald HM et al. J Bone Miner Res. 2018;33(8):1464-1469.

8. Reid IR et al. Lancet. 2014; 11;383(9912):146-55.

9. Mohamad N et al. Clin Interv Aging. 2016;22;11:1317-1324.

10. Shigehara K et al. Aging Male. 2017;20(3):139-145.

11. Colleluori G et al. J Clin Endocrinol Metab. 2021;106(8):e3058-e3068.

12. Otremski I et al. Calcif Tissue Int. 1997;60(5):485-7.

13. Golds G et al. Int J Endocrinol; 2017;2017:4602129.

14. Bischoff-Ferrari HA et al. Osteoporos Int. 2008;19(9):1307-14.

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