Vitamin D, Calcium Supplementation, and Bone Fracture Risk

Osteoporosis can be considered an aging process. In a lifetime, osteoporotic fracture affects about 1 in 2 women and 1 in 5 men aged 50 years or older with hip fracture being the most serious type of osteoporotic fracture. Vitamin D is essential for optimal musculoskeletal health because it promotes calcium absorption, mineralization of bone, and maintenance of muscle function. Vitamin D supplementation in several observational studies have been shown to decrease the risk of fracture. Similarly, calcium supplementation has also been shown to be preventive. However, results from the randomized clinical trials, the gold standard for determining if a given therapy is effective or not are lacking.

Yao and colleagues published a systematic review and meta-analysis and pooled data from large observation studies and randomized clinical trials to answer some key questions. In particular, they wanted to assess the risks of fracture associated with supplementation with vitamin D alone or in combination with calcium in RCTs. To identify relevant studies, they searched several medical literature databases: PubMed, EMBASE, Cochrane Library, and other randomized controlled trial databases. The search was from the start of database until December 31, 2018. They selected observational studies involving at least 200 fracture cases and randomized clinical trials enrolling at least 500 participants and reporting at least 10 incident fractures were included.

They identified 11 observational studies with a total number of 39 141 participants who had total of 6278 fractures, out of which 2367 were hip fractures. When they pooled the study results, they found that each increase of 10.0 ng/mL (ie, 25 nmol/L) in vitamin D was associated with an adjusted rate ratio for any fracture of 0.93 (95% CI, 0.89-0.96) and an adjusted rate ratio for hip fracture of 0.80 (95% CI, 0.75-0.86).

They also identified 11 RCTs of vitamin D supplementation alone enrolling 34 243 participants, 2843 fractures of which 740 were hip fractures. These trials did not find any decrease in risk of any fracture with Vitamin D supplementation alone (rate ratio, 1.06; 95% CI, 0.98-1.14). Similarly, there was no decrease in risk of hip fracture (rate ratio, 1.14; 95% CI, 0.98-1.32).

In contrast, a meta-analysis of 6 RCTs (49 282 participants, 5449 fractures, 730 hip fractures) of combined supplementation with daily vitamin D (daily doses of 400-800 IU) and daily calcium (daily doses of 1000-1200 mg) found a 6% reduced risk of any fracture (rate ratio, 0.94; 95% CI, 0.89-0.99) and a 16% reduced risk of hip fracture (rate ratio, 0.84; 95% CI, 0.72-0.97).

The final word: If you take vitamin D and/or calcium to reduce the risk of osteoporosis and osteoporotic fractures, you should take both calcium and vitamin D supplements together. Taking just one medication is unlikely to decrease fracture risk.

Aspirin and Body Weight

Low dose aspirin has been shown to reduce cardiovascular events but the observed effect may vary by weight. In fact, in one of our studies, we have shown that not only obese individuals had greater baseline platelet reactivity, they also had greater residual platelet reactivity after low-dose aspirin therapy. Comparing obese and nonobese individuals after aspirin therapy, results for aggregometry to collagen were 6.7 vs 6.1 ohms, P=.008; aggregometry to adenosine diphosphate were 13.1 vs 11.8 ohms,P<.0001; aggregometry to arachidonic acid (AA) were 4.9% vs 8.3% nonzero aggregation, P=.002; urinary excretion of 11-dehydro-thromboxane B2 (Tx-M) were 4.9% vs 8.3% nonzero aggregation, P=.002; and aspirin resistance were 26.% vs 20.5%, P=.002; respectively.

Now an individual-patient meta-analysis of primary prevention randomized controlled trials with low-dose aspirin have shown that clinical outcomes are also different in patients with weight>70Kg than in patients with weight<70Kg. On the other hand, when a higher dose of aspirin was examined, individuals with weight>70Kg obtained clinical benefits. Clinical benefits were not limited to cardiovascular outcomes but also included colorectal outcomes.

An obvious implication of such studies is that individuals with weight>70Kg should take perhaps more than one baby aspirin to receive benefit from aspirin.

Struggling Healthcare Organizations

A systematic review identified five characteristics of healthcare organizations that are struggling to improve quality.

1.  Poor organizational culture: Such as limited ownership, not collaborative, hierarchical, with disconnected leadership

2. Inadequate infrastructure: Limited quality improvement, staffing, information technology or resources

3. Lack of a cohesive mission: Mission conflicts with other missions, is externally motivated, poorly defined or promotes mediocrity

4. System shocks: Events such as leadership turnover, new electronic health record system or organizational scandals that detract from daily operations

5. Dysfunctional external relations with other hospitals, stakeholders, or governing bodies.

Designing a RCT and Network Meta-analysis

A review of literature with possible meta-analysis of available data is often recommended before a randomized clinical trial (RCT) can be proposed. This article goes a step further and suggests using network meta-analysis for planning and designing a RCT. Authors emphasize that a trial design based on updating the evidence from a network meta-analysis of relevant previous trials may require a considerably smaller sample size to reach the same conclusion compared with a trial designed and analyzed in isolation.