Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Benefits of Calcium and Vitamin D: A Meta-analysis

In an era of multiple randomized controlled trials that have documented the efficacy of antiresorption agents (eg, alendronate, risedronate, ibandronate, raloxifene) both to enhance bone mineral density (BMD) and reduce osteoporotic fractures, there remains some uncertainty about the efficacy of calcium supplementation, vitamin D supplementation, or the combination. Even meta-analysis on the topic have been inconsistent.

The impact of supplementation is especially important to clarify since in developing nations, which are beginning to share the same 'graying' demographics as America, the cost of preventive treatments is critical.

Tang, et al performed a meta-analysis on all recorded randomized clinical trials of persons over 50 (n=29), comprised of 52,625 participants. The trial selection process can provide greater assurance than earlier meta-analysis, because they did not include any observational trials.

Overall, calcium or calcium plus vitamin D were associated with a 12% relative risk reduction in fracture risk (p=0.0004) in a time span of approximately 3.5 years. Beneficial effects are greatest in the highest risk, elderly, slender population who have low calcium intake at baseline, but is still beneficial in the over-50 population as a whole. Comparing various doses of calcium, more benefit was seen with doses over 1200 mg/day of calcium. Although in the large category of 'any' supplementation with vitamin D, no measurable benefit was seen over calcium supplementation alone. When higher doses of vitamin D were used, there was additional benefit. Outcomes were similar regardless of gender. The authors suggest that calcium and vitamin D, when given at doses of at least 1200 mg/d and 800 IU/d respectively, improves BMD and reduces fractures in persons over 50. Tang BMP, et al. Lancet. 2007;370:657-66.

ARBs and Inflammatory Markers in Type 2 Diabetics

Discussions about the role of inflammation in generating endothelial dysfunction, atherosclerosis, and cardiovascular (CV) endpoints continue to generate interest. Antibiotic therapy has not improved CV outcomes, nor has modulation of homocysteine or antioxidants. NSAIDs, despite being prototypically anti-inflammatory, remain under a dark CV cloud. Perhaps, though, the method by which inflammation is reduced is pertinent. To address this concept further, a study of diabetic hypertensives was performed comparing one year of atenolol (ATN) therapy with valsartan (VAL).

At baseline, inflammatory markers (cytokines, chemokines, and adhesion molecules) were measured in both groups; additionally, a group of nonhypertensive subjects was included for comparison.

Compared with non-hypertensive controls, inflammatory markers were 2-4 fold higher in diabetic hypertensives at baseline. During treatment, glucose and lipid levels did not change, hence any variation in inflammatory markers would not be attributable to enhanced management of diabetes or dyslipidemia.

ATN and VAL lowered blood pressure to a similar degree, but there was disparity in effects upon inflammation: VAL reduced all three categories of inflammatory markers, but only cytokine IL-18 was reduced by ATN.

Treating diabetic hypertension with VAL provides broad reductions of inflammatory markers compared to atenolol. Whether modulation of inflammation will ultimately impact the CV outcomes of hypertension remains to be seen.

Touyz RM, et al. J Am Society of Hypertens. 2007;1(3):189-199.

When Oral Therapy Fails in Type 2 Diabetes

One might assume that the proliferation of tools to manage type 2 diabetes (2DM) would augur well for levels of diabetic control. Unfortunately, that appears to not be the case. The progressive nature of the disease, hesitance of clinicians to advance therapy, reluctance to employ parenteral agents, and growing burden of obesity and sedentary lifestyle all contribute. Thiazolidinediones (TZDs, ie, pioglitazone, rosiglitazone) have shown promise as potent agents to reduce glucose. In the recently published ADOPT trial, durability of glucose control with rosiglitazone monotherapy was found to be superior to other comparators; at 5 years, the failure rate was lowest with rosiglitazone (15%), next lowest with metformin (21%), and greatest with sulfonylurea (34%).

Riedel assessed retrospectively the time to loss of control after adding a TZD to a regimen of either metformin or metformin plus sulfonylurea in a managed care population of diabetics (n=579).

Several interesting insights are provided by this examination of a 'real world' (as opposed to data from a randomized clinical trial) patient population. First, the addition of a TZD did enable the majority to achieve a goal of < 7.0%. Second, the mean time to failure was 1.3 years. Finally, the addition of TZD to metformin provided more durable glucose control than adding sulfonylurea to metformin. Clinicians must remain vigilant for early treatment failure of oral hypoglycemic agents. It happens very quickly in some patients.

Riedel AA, et al. Am J Manag Care. 2007;13:457-463.