Calcium and Vitamin D for RA

Personal Views by Two Dragon Claw Members[1]

based on Google Scholar published research

Quick Summary

The taking of prednisone over time encourages bone density loss.  As one gets older sourcing vitamin D from sunlight may be less efficient and this may encourage your bones to lose some of their strength, all other things being equal.  For older people vitamin D can improve muscle strength. The academic research is somewhat mixed as to how effective vitamin D by itself is to reduce fracture risk.  Vitamin D, however, when taken as a supplement with calcium is effective in reducing bone fracture risk. Too much can have the opposite effect. 

If you are on a biologic for your RA, the impact on bone density is unclear.  The association between RA and an increased risk of heart disease is quite strong.  The benefits of calcium in this group remains controversial.

Current State

The literature associated with vitamin D with or without calcium supplementation on bone density is mixed, though mostly in favour of a beneficial effect of calcium and vitamin D on bone density. The data on the effect of vitamin D and calcium on fracture rates is more variable with some recent larger studies tending to contradict older small sample research.  Most research has been based on female groups but there is growing suspicion that males have a different response. The generally accepted dose is 1000 IU/day leading to a blood concentration of  25 (OH)D level above 50-75 nmol/L (though the optimal concentration is not firmly established and different guidelines have different targets).  A report following a panel conference of world experts[2] in late 2016 indicated that:

  • 53 studies concluded that there is high-quality evidence that vitamin D plus calcium reduces hip fractures by 16% as well as the risk of any type of fracture[3];
  • Vitamin D supplementation alone (without calcium) is unlikely to be effective in preventing hip fractures or fractures of any type;
  • Some trials show that very high dose, intermittent vitamin D (e.g. 500 000 IU yearly, or 60 000 IU monthly) [4]may increase falls and fracture; and
  • Medication treatment of individuals with osteoporosis and/or history of fragility fracture is still the most effective way to prevent future fractures.

Contrary to be above points in 2018 Cummings et al, focusing on people who did not have a deficiency of vitamin D or calcium, stated that "trials of calcium and of vitamin D supplementation in community populations with lesser degrees of calcium and vitamin D deficiency have found lesser or no effect on fracture risk, leading to controversies about the role of calcium and vitamin D supplementation in fracture prevention[5]."  This suggests that the role of replacing vitamin D and calcium in those who already have enough or are not deficient is unclear.

Vitamin D supplementation appears to improve muscle strength at normal dose levels of 1000 IU/day. There is, however, little evidence that bone turnover markers are improved[6].

Biologics and Vitamin D

Studies on the positive effects of biologic drugs on bone mineral density are early, small and somewhat mixed.  Virtually every researchers agrees that prednisolone encourages bone loss. In addition, proton pump inhibitors (PPI), can interfere with calcium absorption. 

  1. Increasing calcium intake from dietary sources or by taking calcium supplements produces small non-progressive increases in bone density, which are unlikely to lead to a clinically significant reduction in risk of fracture. [BMJ 2015;351:h4183; 2015].However, another study suggests that high intake of dairy food benefitted older men more than women.[Res, 33: 1283-1290. doi:1002/jbmr.3414]
  1. From a small population study, IL-6 blocking agents also showed improvement in localized bone loss not seen with anti-TNF agents.And IL-6 blocking agents [tocilizumab] also show improvement in localised bone loss. [Osteoporos Int., DOI 10.1007/s00198-016-3769-2; 2016]

Heart Disease of Calcium

A large USA study suggested that high intake of supplemental calcium is associated with an excess risk of heart disease (CVD) death in men but not in women. [JAMA Intern Med. 2013 Apr 22; 173(8): 639–646. doi: 10.1001/jamainternmed.2013.3283]. However, based on a large UK study there was no evidence that use of calcium/vitamin D supplementation was associated with increased risk of hospital admission or death after ischemic cardiovascular events[7].  A 2016 meta analysis seems to suggest that dose levels play a role: "Calcium intake within tolerable upper intake levels (2000 to 2500 mg/d) is not associated with CVD risk in generally healthy adults". [ Ann Intern Med. doi:10.7326/M16-1165]

Women with RA have a 2-3 fold higher risk of myocardial infarction[8].  Patients with RA for ten years or more, positive Rheumatoid Factor or anti-CCP or presence of certain extra-articular manifestations increases the likelihood of CVD events by 50%[9].   Indeed, a review in the European Heart Journal indicated that 50% of RA patients may have premature deaths attributed to cardiovascular disease[10]. There is a suggestion that the overall risk of CVD in women with rheumatoid arthritis increase their risk by an additional 2% and 4% in men using calcium supplementation.  

These observations have yet to be put to the test in a large population based study but calcium supplementation should be considered cautiously if dietary means of increasing calcium are ineffective.  In other words, get your calcium from a good diet not via supplementation.

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Note:  The Australian Heart Foundation says that in 2017 27% of deaths was due to heart disease.  Clearly, the older you are the higher the risk. Factors which increase risk are high blood pressure, high cholesterol, diabetes, smoking and overweight among others.  Lifestyle factors to reduce the risk are exercise and a good diet.  If you are up to reading a detail scientific article the review by Lazzerini et al, footnote 10 is a key clinical update. Do not act on anything in this article without FIRST speaking to your doctor.

 

[1] MG and Dr. AK

[2] Duque, G. , Daly, R. M., Sanders, K. and Kiel, D. P. (2017), Vitamin D, bones and muscle: myth versus reality. Australasia  J Ageing, 36: 8-13. doi:10.1111/ajag.12408

[3] Avenell A, Mak JC, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures in post‐menopausal women and older men. Cochrane Database Systematic Review. 2014: Cd000227.

[4] 500,000 IU of D3 annually 

[5] Cummings, S. R. and Eastell, R. (2018), A History of Pivotal Advances in Clinical Research into Bone and Mineral Diseases. J Bone Miner Res, 33: 5-12. doi:10.1002/jbmr.3353

[6] Norenstedt, S. , Pernow, Y. , Zedenius, J. , Nordenström, J. , Sääf, M. , Granath, F. and Nilsson, I. (2014), Vitamin D Supplementation After Parathyroidectomy: Effect on Bone Mineral Density—A Randomized Double‐Blind Study. J Bone Miner Res, 29: 960-967. doi:10.1002/jbmr.2102

[7] Harvey, N. C., D'Angelo, S. , Paccou, J. , Curtis, E. M., Edwards, M. , Raisi‐Estabragh, Z. , Walker‐Bone, K. , Petersen, S. E. and Cooper, C. (2018), Calcium and Vitamin D Supplementation Are Not Associated With Risk of Incident Ischemic Cardiac Events or Death: Findings From the UK Biobank Cohort. J Bone Miner Res, 33: 803-811. doi:10.1002/jbmr.3375

[8] Charles-Schoeman C. (2012). Cardiovascular disease and rheumatoid arthritis: an update. Current rheumatology reports14(5), 455–462. doi:10.1007/s11926-012-0271-5

[9] Ibid; and by  Gullick, N and Scott D in Co-morbidities in established rheumatoid arthritis, Best Pract Res Clin Rheumatol. 2011; 25: 469-483

[10] Lazzerini, P. E et al in Systemic inflamation and arrhythmic risks: lessons from rheumatoid arthritis, European Heart Journal. 2017; 38, 1717-1727