Do your patients have a vitamin D deficiency?
Vitamin D facilitates calcium absorption, yet is often overlooked in managing osteoporosis. Here’s how to diagnose and treat a deficiency.
Too often, less-than-optimal bone health in our patients becomes evident only after a fragility fracture occurs later in life. Early identification of those at risk for osteoporosis—including the identification of potential secondary causes, such as vitamin D deficiency—are critical in improving both prevention and treatment strategies.
Human bone is constantly being remodeled. Old bone is resorbed, and new bone is formed through osteoclast and osteoblast activity. During childhood, new bone is formed more quickly than old bone is removed, allowing bones to grow larger and denser. This bone formation continues at a pace faster than resorption until peak bone mass is reached sometime when patients are in their 20s. From this point forward, resorption slowly exceeds formation.
During adulthood, normal bone remodeling takes approximately four months, assuming the person is in the best of health. If osteoporosis is present, the process is markedly slower, taking up to two years. Bone’s most rapid resorption occurs in the first few years after menopause but persists throughout the postmenopausal years. Thus, a higher peak bone mass during a person’s 20s lays a strong foundation for normal physiologic bone loss in the later years of life.
The National Osteoporosis Foundation recommends bone mineral density (BMD) testing in all women aged 65 years and older (regardless of risk factors) and younger women with one or more risk factors other than being white, female, or postmenopausal (Table 1). Table 2 indicates the World Health Organization’s definition of osteoporosis by T-score, and Table 3 summarizes the Foundation’s recommendations for beginning treatment for osteoporosis.
Other known or emerging risk factors While not officially recognized as a risk factor in the National Osteoporosis Foundation criteria, consistent consumption of more than four cups of coffee is thought to heighten the chance of developing the disease, presumably because of the increased renal excretion of calcium caused by caffeine. Since one cup of coffee contains about 80 mg of caffeine, consuming more than 320 mg may eventually be recognized as an additional risk factor for osteoporosis.
Vitamin D deficiency, an additional risk factor not listed in the Foundation’s guidelines, is receiving plenty of attention as a leading cause of secondary osteoporosis. Vitamin D facilitates calcium absorption and plays an integral part in building and maintaining healthy bones.
Vitamin D is a fat-soluble vitamin technically encompassing two molecules—vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). In addition to being derived from food sources, vitamin D is also synthesized by the body when skin is exposed to sunlight. Those with darkly pigmented skin are at higher risk for vitamin D deficiency because the pigment interferes with absorption of sunlight. Obviously, those who get very little exposure to direct sunlight augment their risk.
There is some dispute over whether a correlation exists between living at higher latitudes and developing vitamin D deficiency. One study found that in Boston, very little cholecalciferol was synthesized cutaneously from winter sunlight, indicating a potential influence of season and latitude. However, nearly 80% of one cohort studied in Europe was found to be vitamin D-deficient regardless of whether the participants lived in sun-drenched countries or not. Researchers found the vitamin D levels to be independent of latitude and hypothesized that levels might be low throughout the world.
Obesity is also considered a risk factor in vitamin D deficiency. Vitamin D is fat-soluble and readily stored in adipose tissue, reducing its circulation in the bloodstream. Researchers have studied the capability of obese women to handle vitamin D originating from either oral or cutaneous sources. Since the obese women had more body surface, it was expected they would be able to synthesize more vitamin D from UVB irradiation. But the cholecalciferol concentrations in these women after exposure were 57% lower than their nonobese cohorts. Because there was no difference in vitamin D precursors, researchers believe that release of vitamin D from the skin into the circulation is altered in obese women. Orally supplied, intestinally absorbed ergocalciferol was found to be most bioavailable in the obese.
Use of concomitant medications known to reduce vitamin D metabolism is also a risk factor for osteoporosis. These drugs include phenytoin (Dilantin), carbamazepine (Tegretol), phenobarbital, thiazide diuretics, corticosteroids, and nicotine. Corticosteroids decrease calcium absorption. Anticonvulsants and thiazide diuretics can increase the catabolism of vitamin D, and nicotine blunts vitamin D-stimulated calcium absorption in the intestine.
Patients with chronic kidney disease and/or chronic liver disease are also at risk for osteoporosis via the vitamin D connection. Malabsorption of calcium and vitamin D is associated with most types of chronic liver disease, whereas progressive kidney disease results in reduced vitamin D related to phosphate retention and malabsorption of calcium.
Interrelationship of calcium, vitamin D, and parathyroid hormone
Skeletal health is dependent on the interrelationship between appropriate levels of calcium, vitamin D, and parathyroid hormone (PTH). Calcium stored in the bone is continuously exchanged with calcium circulating in the bloodstream. When calcium intake is sufficient, levels within the bone remain stable. However, when calcium intake is insufficient, the body maintains the serum calcium level at the expense of the bones. In other words, the body will steal calcium from the bone to maintain serum calcium levels.
Vitamin D promotes bone mineralization by increasing calcium absorption in the small intestine. When vitamin D levels are sufficient, dietary calcium absorption is approximately 30%-40%. As vitamin D levels decline, calcium absorption plummets to a mere 10%-15%, triggering release of PTH. High levels of PTH increase bone resorption with a resultant decrease in bone mass. Therefore, any factor that interferes with calcium absorption may contribute to low BMD and osteoporosis (Table 4).
Diagnosing vitamin D deficiency
Symptoms of mild vitamin D deficiency (besides osteoporosis) are nonspecific and include chronic pain and lower-extremity weakness. Symptoms of increasingly severe vitamin D deficiency and hypocalcemia will be more classic, i.e., neuromuscular irritability, including paresthesias, muscle cramps, Chvostek’s sign (facial muscle twitching with cheek percussion), and seizures. In addition to first-tier laboratory workup for secondary causes of osteoporosis, a second round of tests may also be indicated, depending on the patient’s risk factors and clinical presentation (Table 5).
The cut points for diagnosing vitamin D deficiency are in debate, but most experts suggest 25-hydroxyvitamin D (25[OH]D) levels in sufficient quantity to keep PTH well within the normal range. Research indicates that a 25(OH)D level of 32 ng/mL should be the lower limit of normal. A 25(OH)D concentration of <10 is considered a frank deficiency.
Interestingly, the threshold for rickets/osteomalacia is <8. For now, a 25(OH)D level between 10 and 32 is considered an insufficiency. Hopefully, some consensus criteria will be forthcoming.Medical management of osteoporosis and vitamin D deficiency
As with any osteoporosis patient, medical management of those with vitamin D deficiency or insufficiency involves all the usual lifestyle modifications, i.e., adequate calcium intake, weight-bearing exercise, smoking cessation, alcohol in moderation only, caffeine reduction, and fall prevention. In addition, the level of vitamin D needs to be corrected.
Current supplementation guidelines for maintenance of vitamin D (Table 6) are intended to help keep patients in the normal range. As with the cut points for diagnosing vitamin D insufficiency or deficiency, the supplementation recommendations also vary. These guidelines are expected to change soon as well.
Treatment guidelines, on the other hand, are designed to restore patient’s vitamin D to normal levels (Table 7). Vitamin D is available in supplement doses as D3 (cholecalciferol) and in pharmacologic doses as D2 (ergocalciferol). Any concomitant problem that may have contributed to the patient’s vitamin D deficiency must also be addressed if treatment is to be successful.
The average person can typically fulfill daily requirements by eating a diet rich in foods containing vitamin D, such as fortified milk, some fortified cereals, and fatty fish, such as salmon, tuna, herring, and halibut. Diet should be augmented with approximately 10-15 minutes of direct sun exposure every day. For those with darker skin, those who get limited direct sunlight, or those who eat little vitamin D-rich food, a supplement may be required.
Calcium is equally important and is often combined with supplemental vitamin D. Patients should be aware that calcium carbonate requires gastric acid for proper dissolution and absorption in the duodenum and will be better absorbed with meals, when gastric acid secretion is stimulated. Calcium citrate does not require gastric acid for dissolution and absorption and, therefore, is an excellent choice for patients on proton-pump inhibitors.
It goes without saying that lifestyle issues, such as weight-bearing exercise, altering the environment to prevent falls, smoking cessation, and moderate alcohol and caffeine consumption, are also important in rounding out the prevention and management of any type of osteoporosis.
While beyond the scope of this article, other medical management approaches directed specifically at osteoporosis, including antiresorptives or anabolics, will typically be required. A helpful update regarding these therapies and general osteoporosis guidelines can be found online at www.medscape.com/viewarticle/533846 (accessed March 1, 2007). The updated guidelines were also published in Menopause (2006;13:340-367).