Calcium+D may reduce fracture risk

On January 22, 2010, in Fat Solubles, Minerals, Vitamins, by Andrea

Um.  Duh?

But for the 2 of you that have not been paying attention.

Take your calcium (citrate) and D.

From Medscape:

Daily Calcium Plus Vitamin D Supplements May Reduce Fracture Risk

Laurie Barclay, MD

January 22, 2010 — Daily supplements of calcium plus vitamin D, but not of vitamin D alone, are associated with significantly reduced fracture risk, according to the results of a patient level-pooled analysis reported in the January 12 issue of the BMJ.

“A large randomised controlled trial in women in French nursing homes or apartments for older people showed that calcium and vitamin D supplementation increased serum 25-hydroxyvitamin D, decreased parathyroid hormone, improved bone density, and decreased hip fractures and other non-vertebral fractures,” write B. Abrahamsen, from Copenhagen University Hospital Gentofte, in Copenhagen, Denmark, and colleagues from the DIPART (vitamin D Individual Patient Analysis of Randomized Trials) Group.

“Subsequent randomised trials examining the effect of vitamin D supplementation — with or without calcium — on the incidence of fractures have produced conflicting results….We used individual patient data methods to do a meta-analysis of randomised controlled trials of vitamin D — with or without calcium — in preventing fractures and investigated if treatment effects are influenced by patients’ characteristics.”

The goals of the study were to identify characteristics affecting the antifracture efficacy of vitamin D or vitamin D plus calcium regarding any fracture, hip fracture, and clinical vertebral fracture and to evaluate the effects of dosing regimens and coadministration of calcium.

Selection criteria were randomized trials with at least 1 intervention group in which vitamin D was given, in which there were at least 1000 participants, and in which fracture was an outcome. The investigators identified 7 major randomized trials of supplementation with vitamin D plus calcium or with vitamin D alone, enrolling a total of 68,517 participants. Mean age was 69.9 years (range, 47 – 107 years), and 14.7% of participants were men. Significant interaction terms were identified with logistic regression analysis, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and use of hormone therapy and bisphosphonates.

Overall risk for fracture was decreased in trials using vitamin D with calcium (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86 – 0.99; P = .025), and risk for hip fracture was also decreased (HR for all studies, 0.84; 95% CI, 0.70 – 1.01; P = .07; HR for studies using 10 μg of vitamin D given with calcium, 0.74; 95% CI, 0.60 – 0.91; P = .005). There were no significant effects for vitamin D alone in daily doses of 10 μg or 20 μg, nor was there any apparent interaction between fracture history and treatment response. No interaction was noted for age, sex, or use of hormone replacement therapy.

“This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures,” the study authors write. “By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.”

Limitations of this study include lack of data for 4 of the 11 identified studies meeting inclusion criteria, and insufficient information about compliance to do a per protocol analysis. In addition, only a single study provided data for vitamin D given alone at the lower dose.

“We must emphasise that this analysis does not allow for a direct comparison of vitamin D against vitamin D given with calcium, but only comparisons between each intervention and no treatment,” the study authors conclude. “Whether intermittent doses of vitamin D given without calcium supplements can reduce the risk of fractures remains unresolved from the studies in this analysis. Additional studies of vitamin D are also needed, especially trials of vitamin D given daily at higher doses without calcium.”

In an accompanying editorial, Dr. Opinder Sahota, from Queen’s Medical Centre in Nottingham, United Kingdom, notes that these findings are important because they show that vitamin D alone, irrespective of dose, does not reduce the risk for fracture.

“Although the evidence is still confusing, there is growing consensus that combined calcium and vitamin D is more effective than vitamin D alone in reducing non-vertebral fractures,” Dr. Sahota writes. “Higher doses are probably necessary in people who are more deficient in vitamin D, and treatment is probably more effective in those who maintain long term compliance. Further studies are needed to define the optimal dose, duration, route of administration, and dose of the calcium combination.”

The National Heart, Lung, and Blood Institute, National Institutes of Health, supported this study. Some of the study authors have disclosed various financial relationships with Novartis, Amgen, Nycomed, Eli Lilly, Procter & Gamble, Merck, Roche, Shire, ProStrakan, Servier, Celltech, ProStrakan, Alliance for Better Bone Health, GlaxoSmithKline, Pfizer, Sanofi-Aventis, and/or Osteologix.

Dr. Sahota has disclosed no relevant financial relationships.

BMJ. 2010;340:b5463.

Great!  Something that all RNY patients need to hear.. a study that links pernicious anemia — a condition that results from a low level of B12 leading to a form of anemia that is very common in post-RNY patients and hip fracture — something that is already a heightened risk due to the malabsorption of vitamin D and calcium.


I’m so screwed…

From Medscape:

Hip Fracture Risk Elevated With Pernicious Anemia: Study

Megan Brooks

January 8, 2010 — Patients with pernicious anemia have significantly higher risks for hip fracture, research shows.

Compared to age- and sex-matched controls, patients with pernicious anemia had a 73% greater risk of hip fracture (3.4 vs. 2.0 hip fractures/1000 person-years of follow-up). The elevated risk was even greater with newly diagnosed pernicious anemia (HR, 2.63).

“These data suggest that physicians need to carefully follow the bone health of patients with pernicious anemia,” senior author Dr. Yu-Xiao Yang of the University of Pennsylvania School of Medicine in Philadelphia noted in an email to Reuters Health.

Additionally, Dr. Yang and colleagues found that the increased risk of hip fracture persisted for many years even after vitamin B12 repletion therapy was started.

“Physicians should recognize that correction of their vitamin B12 deficiency alone is probably insufficient in reducing the risk of fractures in these patients. The persistent nature of the elevated fracture risk in these patients suggests the presence of underlying mechanisms independent of vitamin B12 deficiency,” Dr. Yang said.

There are physiologic reasons to suspect that patients with pernicious anemia (who are by definition achlorhydric) may have impaired bone strength and increased fall risk (i.e., due to vitamin B12 deficiency), but there have been no definitive epidemiologic data to confirm an increased fracture risk in these patients, the researcher explained.

The new findings stem from an analysis of data from the United Kingdom’s General Practice Research Database. Included were 9506 adults with pernicious anemia who received vitamin B12 therapy for at least 1 year. Each case patient was matched with four controls without pernicious anemia (n = 38,024). The average follow-up time in both groups was slightly more than 5 years.

As reported online December 18 in Gastroenterology, the increased risk of hip fracture appeared to persist well beyond 5 years after the diagnosis of pernicious anemia and initiation of vitamin B12 therapy. Pernicious anemia was associated with a threefold increased risk of hip fracture when follow-up years 3 through 10 were combined in the analysis.

“One potential mechanism,” Dr. Yang said, “may be related to the achlorhydria-induced hypergastrinemia in these patients that could lead to parathyroid hyperplasia, which could result in increased parathyroid hormone secretion or altered parathyroid hormone secretion pattern.”

Another possibility is that their lack of gastric acid may compromise calcium absorption in the intestine. “Therefore,” Dr. Yang advised, “physicians should at least ensure that these patients maintain daily recommended calcium intake appropriate for their age, and preferably by taking water-soluble calcium supplements (e.g., calcium citrate) or through dairy products. If they must take water-insoluble calcium supplements (e.g., calcium carbonate), they should take them with a meal.”

Both of these potential mechanisms, Dr. Yang noted, may also be relevant to the reported association between acid suppressive therapy and increased risk of fractures.

“Further research is urgently needed to investigate these potential mechanisms so that effective preventive measures can be developed both for patients with pernicious anemia and for the large population of patients who require chronic acid suppressive therapy,” he concluded.

Gastroenterology. Published online December 18, 2009. Abstract

Reuters Health Information 2010. © 2010 Reuters Ltd.

Monitor Bone Density Carefully after WLS

On December 25, 2009, in Minerals, by Andrea

This is somewhat old — 12/2008, and we know more about D, PTH, and such these days.  But still, it’s there and it’s important.

From Medscape:

Monitor Bone Density Carefully After Bariatric Surgery

Ann J. Davis, MD

BMD and serum calcium levels dropped following bariatric surgery in morbidly obese men and women.


Despite the benefits associated with long-term weight loss that are achievable with bariatric surgery, such procedures lead to abnormal bone and mineral metabolism. In a prospective 1-year study, researchers evaluated bone metabolism and BMD in 23 morbidly obese men and women (mean BMI, 47 kg/m2) who underwent Roux-en-Y gastric bypass (RYGB) surgery, which is the most commonly performed bariatric surgery procedure. Following surgery, patients who were ≤50 were prescribed 1500 mg calcium citrate and 600 IU vitamin D daily; older patients were prescribed 1800 mg calcium citrate and 800 IU vitamin D daily. Eighteen participants were women, 7 of whom were postmenopausal.

Overall, mean weight loss was 45 kg during the first postoperative year, and mean BMI dropped to 31. At 12 months, mean BMD had declined by 9.2% at the femoral neck and 8.0% at the total hip, but mean BMD at the lumbar spine had not changed significantly. Degree of BMD attenuation correlated strongly with extent of weight loss. Despite supplementation of calcium and vitamin D intake, urinary calcium dropped, and serum hydroxylated vitamin D concentrations remained unchanged.


Although these findings should concern us, the relative effects of bariatric surgery and preexisting conditions such as vitamin D deficiency (common in obese patients) have been difficult to separate, especially because previous studies have been cross-sectional rather than longitudinal. Calcium absorption occurs mainly in the duodenum, which is bypassed in RYGB surgery; therefore, results might differ for other bariatric procedures. Nevertheless, monitoring for nutritional deficiencies and BMD is particularly important in women who undergo duodenal bypass procedures.


  1. Fleischer J et al. The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss. J Clin Endocrinol Metab 2008 Oct; 93:3735.