Vitamin D needs calcium supplementation for preventing fracture: JAMA

Delhi: Daily supplementation with both vitamin D and calcium is a more promising strategy for reducing fracture risk compared to vitamin D supplementation alone, reveals a recent review study published in JAMA Network Open.

Osteoporosis is characterized by reduced bone mass and fragmentation of bone architecture, resulting in an increased risk of fracture. Vitamin D is essential for musculoskeletal health due to its role in calcium absorption, mineralization of osteoid tissue formation in bone, and the maintenance of muscle function. Low vitamin D causes secondary hyperparathyroidism, bone loss, and muscle weakness.

Vitamin D and calcium supplements are recommended for the prevention of fracture, but previous randomized clinical trials (RCTs) have reported conflicting results. Also, there is uncertainty about optimal doses and regimens for supplementation and their overall effectiveness.

Pang Yao, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom, and colleagues conducted assessed the risks of fracture associated with differences in concentrations of 25-hydroxyvitamin D (25[OH]D) in observational studies and the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs.

The researchers searched the online databases from database inception until December 31, 2018. Searches were performed between July 2018 and December 2018. Observational studies involving at least 200 fracture cases and RCTs enrolling at least 500 participants and reporting at least 10 incident fractures were included. Randomized clinical trials compared to vitamin D or vitamin D and calcium with control.

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Key findings of the study include:

• In a meta-analysis of 11 observational studies (39 141 participants, 6278 fractures, 2367 hip fractures), each increase of 10.0 ng/mL (ie, 25 nmol/L) in 25 (OH)D concentration was associated with an adjusted RR for any fracture of 0.93 and an adjusted RR for hip fracture of 0.80.


• A meta-analysis of 11 RCTs (34 243 participants, 2843 fractures, 740 hip fractures) of vitamin D supplementation alone (daily or intermittent dose of 400-30 000 IU, yielding a median difference in 25[OH]D concentration of 8.4 ng/mL) did not find a reduced risk of any fracture (RR, 1.06) or hip fracture (RR, 1.14), but these trials were constrained by infrequent intermittent dosing, low daily doses of vitamin D, or an inadequate number of participants.


• In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with vitamin D (daily doses of 400-800 IU, yielding a median difference in 25[OH]D concentration of 9.2 ng/mL) and calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (RR, 0.94) and a 16% reduced risk of hip fracture (RR, 0.84).

"The available evidence from completed RCTs provided no support for the effects of vitamin D alone on the prevention of fracture," wrote the authors. "However, there is a need for meta-analyses of ongoing RCTs assessing the effects of higher daily doses of vitamin D on fracture risk before making recommendations on the use of vitamin D for fracture prevention."

"Further RCTs are needed to assess the efficacy and safety of higher daily doses of vitamin D with calcium in high-risk individuals for prevention of fracture," they concluded.

The study, "Vitamin D and Calcium for the Prevention of Fracture: A Systematic Review and Meta-analysis," is published in JAMA Network Open.

DOI: 10.1001/jamanetworkopen.2019.17789