Patients on steroids must have Vit D levels checked

Posted on October 5, 2011 by Dr. Jonathan

A study just published in The Journal of Clinical Endocrinology & Metabolism alerts clinicians to the need for vigilance in attending to vitamin D levels for patients on chronic steroid medication. The authors state:

“In many disorders requiring steroid therapy, there is substantial decrease in bone mineral density. The association between steroid use and 25-hydroxyvitamin D [25(OH)D] deficiency has not been confirmed in large population-based studies, and currently there are no specific vitamin D recommendations for steroid users…The aim of the study was to evaluate the association of serum 25(OH)D deficiency [defined as 25(OH)D <10 ng/ml] with oral steroid use.”

They performed a cross-sectional analysis on a nationally representative sample of 22,650 U.S. children and adults from the NHANES study. (This is considered representative of 286 million U.S. residents.) It’s not clear why they set the bar so high, but their main outcome measure was serum 25(OH)D levels below 10 ng/ml which is a severe deficiency. What did the data show?

“A total of 181 individuals (0.9% of the population) used steroids within the past 30 d. Overall, 5% of the population had 25(OH)D levels below 10 ng/ml. Among steroid users, 11% had 25(OH)D levels below 10 ng/ml, compared to 5% among steroid nonusers. The odds of having 25(OH)D deficiency were 2-fold higher in those who reported steroid use compared to those without steroid use. This association remained after multivariable adjustment and in a multivariable model using NHANES III data.”

It’s a bit of a jolt to know that as many as 5% of the US population has 25(OH)D levels below 10 ng/ml. The risk is doubled for those on chronic steroids. The authors conclude:

“Steroid use is independently associated with 25(OH)D deficiency in this nationally representative cohort limited by cross-sectional data. It suggests the need for screening and repletion in patients on chronic steroids.”

The highest amounts of calcium intake increase the risk of fracture

Posted on May 28, 2011 by Dr. Jonathan

Patients are often surprised to learn that osteoporosis is not a calcium deficiency disorder but rather a failure to maintain the microarchitecture of the bone of which the protein matrix is a critical component. Moreover, earlier posts on magnesium and calcium have document the pro-inflammatory potential of calcium supplementation. Now fascinating research just published in the British Medical Journal offers evidence that calcium above the lowest quintile does not improve the risk of fracture of any type, while the highest levels actually increase the risk of fracture. The authors set out to…

“……investigate associations between long term dietary intake of calcium and risk of fracture of any type, hip fractures, and osteoporosis.”

They note that confusion regarding the issue of calcium requirements has been…

“…reflected by the wide range of daily calcium recommendations for individuals older than 50 years: at present 700 mg in the UK, 800 mg in Scandinavia, 1200 mg in the United States, and 1300 mg in Australia and New Zealand.”

The authors investigated 61,433 women born between 1914 and 1948 for 19 years for correlations between dietary intake of calcium and fractures of any type, hip fractures, and osteoporosis. They took into consideration vitamin D consumption, hormonal status, and other pertinent biological and lifestyle factors including physical activity. Perhaps not surprisingly in light of other evidence that has emerged recently about calcium, their data challenges the conventional wisdom:

“These findings show an association between a low habitual dietary calcium intake (lowest quintile) and an increased risk of fractures and of osteoporosis. Above this base level, we observed only minor differences in risk. The rate of hip fracture was even increased in those with high dietary calcium intakes.“

In others, amounts higher than the lowest level of calcium intake adequate to avoid gross insufficiency and compromised bone micoarchitecture there were not only no significant benefits, the highest levels of intake increased fracture risk. The authors comment:

“The present results may reflect a situation when a moderate intake of calcium* combined with adequate intake of other micronutrients is sufficient to meet the structural and functional demands of the skeleton. High levels of intake did not further decrease the rate of fracture, and might even increase the rate of hip fractures…Moreover, use of supplemental calcium has been associated with higher rates of hip fracture both in a cohort study and in randomised controlled trials…Furthermore, high calcium doses slow bone turnover and also reduce the number of active bone remodelling sites. This situation can lead to a delay of bone repair caused by fatigue, and thus increase the risk of fractures independent of bone mineral density.”

*Their data indicate that a total dietary intake of 700 mg of calcium per day is sufficient to prevent fracture and osteoporosis. The authors conclude:

“Incremental increases in calcium intake above the level corresponding to the first quintile of our female population were not associated with a further reduction of osteoporotic fracture rate.”

Considering that chronic inflammation can be a primary factor in causing loss of the protein ‘scaffolding’ of bone responsible for strength, resilience, and the matrix to which minerals attach, these findings invoke recollection of the recent evidence that calcium supplementation can increase the inflammation of cardiovascular disease. In case you missed it, a recent research paper published in the British Medical Journal follows up on earlier reports of this association. The authors’ intent was…

“To investigate the effects of personal calcium supplement use on cardiovascular risk in the Women’s Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study), using the WHI dataset, and to update the recent meta-analysis of calcium supplements and cardiovascular risk.”

The examined the data from a randomised, placebo controlled trial of calcium alone or with vitamin D in 36,282 postmenopausal women over seven years for myocardial infarction, coronary revascularisation, death from coronary heart disease, and stroke. The data told an interesting story:

“In the WHI CaD Study there was an interaction between personal use of calcium supplements and allocated calcium and vitamin D for cardiovascular events…Calcium or calcium and vitamin D increased the risk of myocardial infarction (relative risk 1.24 (1.07 to 1.45), P=0.004) and the composite of myocardial infarction or stroke (1.15 (1.03 to 1.27), P=0.009).”

Clinicians and patients need to appreciate that inflammation, a fundamental causal factor in both osteoporosis and cardiovascular disease, can be made worse by calcium supplements. The authors conclude:

“Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.“

Osteoporosis and autoimmune inflammation

Posted on January 11, 2011 by Dr. Jonathan

Most readers here are well aware that osteoporosis results from a failure to maintain the resilient protein matrix (web, or ‘scaffolding’) of bone tissue, and that chronic inflammation is a prime contributor. A paper just published in Current Opinion in Endocrinology, Diabetes and Obesity examines the role of autoimmunity, now so widespread, in skeletal disease in general and osteoporosis in particular. The authors state:

“There is an increased risk of osteoporotic fractures and osteonecrosis often at a young age among patients with certain systemic autoimmune diseases. The loss of bone mineral density and bone integrity seen with these diseases often cannot be explained by traditional risk factors alone…”

The review studies that document that in rheumatoid arthritis the risk of osteoporosis is doubled, the risk for hip fracture is doubled or tripled, and there is a two to six-fold risk of vertebral fracture.

“Reduction in bone mineral density in RA may be influenced by immobility, inflammation associated with osteoclast activation, and medications used to treat the disease such as corticosteroids.”

In the case of lupus…

“Risk factors for osteoporosis in patients with SLE include high disease activity, vitamin D deficiency, renal disease, corticosteroid use, and premature ovarian failure from cytotoxic medications…”

The include a review of vitamin D in skeletal health and note that besides its well-known role in bone metabolism…

“…vitamin D is thought to have an immunomodulatory function, with deficient levels associated with impaired innate immune function and overexuberant adaptive immune function. Markers of inflammation have been associated with increased bone turnover and bone loss, a factor that is thought to be particularly at play among patients with inflammatory diseases. Consequently, low vitamin D levels can lead to accelerated bone loss among patients with inflammatory diseases. Put together, these observations move us beyond the calcitropic effects of vitamin D deficiency among patients with inflammatory diseases, and argue in favor of higher serum levels than are currently accepted.“

Importantly, the mechanisms by which inflammation disrupts skeletal are becoming known:

“Several studies have found an association between pro-inflammatory cytokines which play a role in bone resorption, such as TNF-α, IL-1 and IL-6, and the development of osteoporosis. Epidemiologic studies have shown levels of systemic inflammation to predict bone loss and future fracture. It is becoming clear that T cells play a pivotal role in regulating bone homeostasis through direct interactions with bone marrow, stromal cells and osteoblasts. Once activated, these T cells release osteoclastogenic cytokines and Wnt ligands.”

And it appears that steroid treatment does not undo the skeletal effects of inflammation:

“Among a cohort of 20 patients with SLE who had never been on steroids, osteocalcin levels were significantly lower, the urinary excretion of cross-links were significantly higher than in a non-SLE cohort, suggesting that there is decreased bone formation and increased bone resorption among steroid-naive SLE patients. Although these findings were attributed to the underlying disease, comparable results were detected among a steroid-treated cohort implying that steroid treatment does not undo the skeletal effects of inflammation in SLE as was speculated by some researchers.”

Summing up the studies linking osteoporosis to SLE, the authors state:

“These findings suggest that patients with more active inflammation are at greater risk for bone loss.“

Concerning the importance of vitamin D and autoimmunity, they comment:

“In light of the alarming prevalence of vitamin D deficiency seen worldwide, all patients with autoimmune disease should have at least a baseline screening 25-hydroxyvitamin level to screen for vitamin D deficiency. The only laboratory test usually required to ascertain the patient’s status is the 25-hydroxyvitamin D level with a goal of at least greater than 30 ng/ml.”

Their conclusion is heightened in significance by the sharp increase in autoimmune disorders in recent years:

“Bone loss and damage commonly occurs in patients with systemic autoimmune diseases. We are improving in our ability to diagnose and treat autoimmune diseases and their complications; yet osteoporosis and osteonecrosis remain growing comorbid conditions.”

Olive oil for age-related bone loss and osteoporosis

Posted on September 28, 2010 by Dr. Jonathan

Yet another reason to consume olive oil was presented in a paper just published in the journal Osteoporosis International. The authors observe…

“Age-related bone loss is associated with osteoblast [cells that build up bone] insufficiency during continuous bone remodeling. It has been suggested that the formation of osteoblasts in bone marrow is closely associated with adipogenesis [production of fat], and age-related changes in this relationship could be responsible for the progressive adiposity of bone marrow which occurs with osteoporosis. In addition, the consumption of oleuropein, a major polyphenol in olive leaves and olive oil, has been associated with a reduction in bone loss.“

They examined the effects of oleuropein on the processes of osteoblastogenesis and adipogenesis in mesenchymal stem cells (MSCs) from human bone marrow. What did they find?

“The results show an increase in osteoblast differentiation and a decrease in adipocyte differentiation when there is oleuropein in the culture media. The gene expression of osteoblastogenesis markers…was higher in osteoblast-induced oleuropein-treated cells….Oleuropein in MSCs induced adipocytes to produce a decrease in the expression of the genes involved in adipogenesis…”

In other words, oleuropein in olive oil appears to be a ‘genetic response modifier’ that promotes healthy bone build-up while inhibiting fat formation. The authors conclude:

“Our data suggest that oleuropein, highly abundant in olive tree products included in the traditional Mediterranean diet, could prevent age-related bone loss and osteoporosis.“

Calcium supplements increase risk of heart attack

Posted on July 30, 2010 by Dr. Jonathan

Important research was just published in the British Medical Journal that adds more weight to the evidence that calcium supplementation is poorly advised for osteoporosis. The authors’ intent was to:

“…investigate whether calcium supplements increase the risk of cardiovascular events.”

They undertook a meta-analysis of cardiovascular events mined from a massive amount of data accumulated in numerous randomised trials of calcium supplements. When the numbers were crunched a 30% increase in myocardial infarctions (heart attacks) was associated with the calcium supplementation. Their conclusion is compelling:

“Calcium supplements (without coadministered vitamin D) are associated with an increased risk of myocardial infarction. As calcium supplements are widely used these modest increases in risk of cardiovascular disease might translate into a large burden of disease in the population. A reassessment of the role of calcium supplements in the management of osteoporosis is warranted.“

This is not surprising if you know that calcium has a competitive edge over magnesium for absorption. Magnesium is critically important for supporting parasympathetic nervous system tone and healthy heart rate variability. It has also been called “nature’s calcium channel blocker” (a class of medications used to treat coronary artery spasm). Moreover, osteoporosis is not a calcium deficiency disorder—it is a problem of calcium utilization due to inflammation and an associated dysregulated hormonal milieu. The authors of an accompanying editorial in the same journal state:

“In the meantime, on the basis of the limited evidence available, patients with osteoporosis should generally not be treated with calcium supplements, either alone or combined with vitamin D, unless they are also receiving an effective treatment for osteoporosis for a recognised indication. Research on whether such supplements are needed as an adjunct to effective agents is urgently required.”

Proton pump inhibitors to suppress stomach acid increase risk of fracture and infection

Posted on May 12, 2010 by Dr. Jonathan

A collection of studies published in the latest edition of Archives of Internal Medicine highlights what you may already know about the dangers of powerfully suppressing digestion in the stomach by inhibiting the production of gastric acid with medications like Prilosec, Prevacid, Nexium, etc. As an accompanying editorial notes:

“A staggering 113.4 million prescriptions for proton pump inhibitors (PPIs) are filled each year, making this class of drugs, at $13.9 billion in sales, the third highest seller in the United States…it should come as no surprise that PPIs have been shown to be overprescribed; between 53% and 69% of PPI prescriptions are for inappropriate indications.”

What kind of damage can be done? Stomach acid is mandatory for the digestion of protein. Protein makes of the flexible matrix (“scaffolding”) of bone to which the minerals attach, so the first study that associates proton pump inhibitors with total fractures is not unexpected:

“Use of PPIs was…modestly associated with clinical spine, forearm or wrist, and total fractures.”

Stomach acid is also the body’s first line of defense against gastrointestinal infections. Two additional papers confirm that PPIs are associated with increased risk of Clostridium difficile infection. The authors of the first paper observe:

“Proton pump inhibitors (PPIs) are widely used gastric acid suppressants, but they are often prescribed without clear indications and may increase risk of Clostridium difficile infection (CDI). We sought to determine the association between PPI use and the risk of recurrent CDI.”

What did their data show?

“Proton pump inhibitor use during incident CDI treatment was associated with a 42% increased risk of recurrence.”

The authors of the second paper reached the same conclusion:

“Increasing levels of pharmacologic acid suppression are associated with increased risks of nosocomial C difficile infection. This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection.”

There is an important difference between treating the underlying causes of conditions like gastroesophageal reflux (which often occurs with stomach acid that is abnormally low) and just suppressing acid production. These studies only scratch the surface of the problems that can occur when the capacity to digest protein and protect the GI tract from infection is suppressed.

Fractures and other complications of osteoporosis drugs

Posted on December 16, 2009 by Dr. Jonathan

Fosamax (Alendronate) and similar medications increase the appearance of bone density on scans by killing off the specialized bone cells (osteoclasts) that do the important jobs of bone resorption and turnover. Problem: balanced turnover is necessary for bones to remain healthy and flexible. The deceptive increase in density masks underlying brittleness that can predispose to fracture and other complications, including Osteonecrosis of the jaw (the jawbone suffers a non-healing internal fracture). Here are just a few studies that highlight the alarming consequences of long-term use of these agents:

There is a better way. The functional medicine approach quantifies the risk factors for osteoporosis: inflammation, hormone regulation and metabolism—and measures bone turnover with a simple urine test—on a personal basis. Prevention and treatment based on these objective findings is safe and wholesome; effectiveness is validated by follow-up tests. Remember: osteoporosis is not a calcium deficiency disorder, but a loss of the bone’s protein ‘scaffolding’. Contact us for more information. Questions?