February 2012

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Vitamin D and Bone Health

Vitamin D is essential for human calcium and phosphorus balance attainment and key to maintenance of musculoskeletal health. Without enough vitamin D, bones weaken and fracture risk increases. Over the past decade, researchers and experts in the field have warned of a “silent epidemic” of vitamin D deficiency in the United States. And yet, in 2010 the Institute of Medicine (IOM) reported that, rather than an epidemic, vitamin D deficiency is not a problem for the majority of Americans. The most recent NHANES data on vitamin D status in the U.S. population published by the National Center for Health Statistics (NCHS)  indicates that, based on IOM definitions of adequacy, two-thirds of the U.S. population had sufficient vitamin D, about one-quarter was at risk of vitamin D inadequacy and another 8% was at risk of vitamin D deficiency.[1]

So is vitamin D deficiency an epidemic or not? Put simply, it depends on how you define your terms: specifically, what blood level constitutes vitamin D insufficiency in an otherwise healthy population. IOM and NCHS reports rest on defining insufficiency as 25-hydroxyvitamin D [25(OH)D] blood levels below 20 ng/mL (<50 nmol/L), while specialty societies such as the Endocrine Society and the National Osteoporosis Foundation define insufficiency as 25(OH)D ≤30 ng/mL (<75 nmol/L). This may seem like a small difference but it has huge public health ramifications, essentially in defining the difference between sickness and health in 50% of the population.

All sides of the debate agree that in certain populations vitamin D insufficiency and deficiency are widespread. Identifying patients at risk requires recognizing the factors that influence vitamin D synthesis, intake, and metabolism. Once a patient is found to be deficient, the decision has to be made as to how much supplemental vitamin D should be given, in what form, and for how long. In these areas, emerging data exist to aid practitioners.
In this issue of Osteoporosis: Clinical Updates, we will discuss the role of vitamin D in skeletal health, its sources, daily requirements, upper safe limits, and potential future applications in building and maintaining strong bones throughout the lifespan.

THE ROLE OF VITAMIN D IN BONE HEALTH

Vitamin D is one of several specific fat-soluble steroids that when metabolized facilitate the absorption and regulation of calcium and phosphorus. There are two forms of vitamin D: D2 and D3. The vitamin D2 form (ergocalciferol) is found in small amounts in certain plants and made commercially by UV irradiation of mushrooms and yeast. Vitamin D2 is a form commonly used in supplements and fortified foods. The vitamin D3 form (cholecalciferol) is synthesized in the skin of vertebrates in response to exposure to ultraviolet B (UVB) radiation either from the sun or from a synthetic light source. Vitamin D3 is the form available from animal foods such as fatty fish, egg yolks, and liver. Chemically synthesized vitamin D2 and vitamin D3 are produced commercially to fortify foods and to be used as dietary supplements.

Vitamin D Synthesis and Activation

Both vitamin D2 and D3 are biologically inactive, whether obtained through UVB exposure, diet, or supplements. They go through a two-step process of hydroxylation, first in the liver, where the parent compound D is converted to 25-hydroxyvitamin D [25(OH)D], known as calcifidiol, and second in the kidney, where it becomes the biologically active form 1,25-dihydroxyvitamin D [1,25(OH)2D] or calcitriol. Calcitriol is a hormone that promotes active intestinal calcium and phosphate transport to be used for bone formation and remodeling.

Figure 1.Vitamin D is produced in the skin and converted to active metabolites in the liver and kidney.

Is one form of vitamin D superior to the other in promoting healthy circulating D levels in the blood? For many years vitamin D2 and vitamin D3 were considered equivalent for humans. Then two small studies reported findings that appeared to give vitamin D3 the advantage, raising concerns about the bioequivalence of orally ingested of vitamin D2. [2, 3] The studies’ observations suggested that vitamin D2 had roughly half the potency of D3 in raising low serum 25(OH)D levels and maintaining them over time. Following these reports, a randomized placebo controlled clinical trial was undertaken to investigate the question. Trial data seem to have settled the controversy for now, observing equivalence between vitamin D2 and D3 in elevating and supporting serum levels of 25-hydroxyvitamin D.[4] The study’s authors speculate that potency differences seen in the earlier reports may result from artifacts of vitamin D formulations used, dosage amounts, and dosing intervals/durations.[4]

In the body, activated vitamin D regulates absorption of calcium from the gastrointestinal system and mobilization of calcium from bone. The activation of 25(OH)D to 1,25(OH)2D is stimulated by high serum parathyroid (PTH) and low phosphorus. It is inhibited by the protein hormone, fibroblast growth factor 23 (FGF23), which is produced by bone. Adequate calcium absorption depends on adequate levels of 25(OH)D. When a person’s 25(OH)D status is sufficient, absorption of dietary calcium is approximately 30-40 percent.[3] As 25(OH)D levels decline, absorption of dietary calcium declines to about 10-15 percent.[3] Maximum absorption of dietary calcium occurs at a 25(OH)D level of 32 ng/mL or higher.[5,6]

As well as leading to decreased calcium absorption, low levels of vitamin D lead to increased release of PTH (secondary hyperparathyroidism), which increases bone resorption and decreases bone mass leading to mineralization defects and fractures. [7] Levels of PTH rise when 25(OH)D levels drop below 30 ng/mL and PTH is often above normal (>65) at levels of serum 25(OH)D less than 20 ng/mL.

National Osteoporosis Foundation Vitamin D Recommendations

To guide clinical decision making, NOF uses the following definitions in its vitamin D recommendations:

In individuals at risk for osteoporosis, fractures, vitamin D deficiency, or insufficiency, vitamin D should be supplemented in amounts sufficient to bring the serum 25(OH)D level to 30 ng/ml (75 nmol/L) or higher. Based on currently available data, the target 25(OH)D level of 30 ng/ml is considered the optimal level for preventing bone degradation. Additional research is needed to further confirm optimal 25(OH)D levels for bone health.

Factors that Affect Vitamin D Levels

A wide range of factors influence the intake, production, and metabolism of vitamin D and thereby contribute to serum levels. Primary among these are exposure to sunlight, dietary intake, absorption in the digestive tract, and conversion to metabolites 25(OH)D and 1,25(OH)2D in liver and kidney, respectively.

Sunlight Exposure

Exposure to UVB radiation from the sun (or a synthetic light source) converts 7-dehydrocholesterol (provitamin D3) in the skin to previtamin D3 which, in turn, becomes vitamin D3. Factors that affect the skin’s ability to synthesize vitamin D are many. Two intrinsic factors that affect vitamin D production are age (the basal layer of the skin where vitamin D is photosynthesized gets thinner with age) and skin pigmentation (higher melanin means lower UVB penetration of the skin).[8] It is not apparent, however, that people with dark skin suffer adverse health consequences as a result of lower epidermal synthesis of vitamin D. For example, despite melanin-antagonized photosyntheis of vitamin in the skin, African Americans have a lower risk of osteoporotic fracture than do Caucasians despite epidemiologic evidence of high rates of 25(OH)D insufficiency.[9, 10] The most likely explanation for this is that African Americans inherently have higher peak bone mass that Caucasians. As a result, they can lose more bone before crossing the fragility fracture “threshold.”

Figure 2. Vitamin D Intake did not reach 400 IU/day for women 50 years and older, even with supplementation.

Extrinsic factors that impede vitamin D synthesis include lifestyle barriers (staying indoors or covering skin with clothing to limit exposure) and UVB intensity (cloud cover and pollution). Surprisingly, studies show that latitude does not appear to affect overall vitamin D synthesis.[11] The winter shortfall in sunlight exposure at northern latitudes appears to be made up during the rest of the year. Theoretically, properly applied and replenished sunscreen would significantly reduce the skin’s exposure to UVB rays. However, research indicates that in practice most people don’t use enough sunscreen or reapply it often enough to completely block their exposure to UVB and production of vitamin D.[12, 13]

Estimates for adequate UVB exposure range from 5 to 30 minutes of sunlight twice a week on the bare face, arms, legs, or back. Commercial tanning beds with an emission of 2-6% UVB used in moderation are roughly equivalent although not recommended in teens or young adults due to skin cancer risk associated with excess UVB exposure.[14, 15]

Dietary Intake

As discussed earlier, dietary sources of vitamin D are limited. The better sources of D3 include fatty fish (herring, mackerel, catfish, salmon), fish liver oil, and to a lesser degree cheese, egg yolks, and liver. Mushrooms are the only plant source of vitamin D2 commonly ingested by humans. Vitamin D2 available from mushrooms varies widely – from 3 IUs per 84-gram serving in raw crimini mushrooms to 943 IUs in raw maitake mushrooms. Exposure to UVB light increases mushroom vitamin D2 content. The increase can be substantial. For example, unexposed portabella mushrooms contain approximately 12 IUs per serving, while portabellas exposed to UVB light contain approximately 493 IUs per serving.[16] In addition to these sources, dairy, margarine, cereal, and orange juice are regularly fortified with vitamin D with their content labeled on packaging.

A diet chronically low in vitamin D coupled with inadequate sunlight exposure over time can lead to vitamin D deficiency. People with diets that restrict their intake of vitamin D-rich foods, such as those with dairy allergies, lactose intolerance, or ovo-vegetarian and vegan diets, are at increased risk of vitamin D deficiency.

Absorption and Conversion Factors

Even with sufficient dietary intake, patients who have conditions that compromise the absorption or conversion of vitamin D, may not gain the benefit of the vitamin D in the foods they eat. Conditions such as cystic fibrosis, Crohns disease, or colitis can cause malabsorption of vitamin D and other nutrients in the digestive tract, while kidney disorders can disrupt the conversion of vitamin D into its active form.

Evidence regarding the effects of gastric bypass surgery on vitamin D absorption are inconclusive to date, with some data suggesting increase and some indicating attenuation in vitamin D levels following surgery.[17, 18, 19] Because vitamin D is fat soluble, it is stored in fat. As a result, body mass index (BMI) 30 or over is associated with lower serum 25(OH)D than BMI in the healthy range. In obese individuals, more vitamin D is sequestered in fat and less released into the bloodstream. Such individuals may need higher intake levels to compensate.[20]

At Risk for Vitamin D Deficiency

Many medications and over-the-counter remedies can adversely interact with vitamin D. Some medications can interfere with vitamin D absorption and/or metabolism. Other medications can have their absorption and/or effects intensified by combination with vitamin D. Potential interactions to be aware of include:

Before prescribing vitamin D supplementation, a careful medication review is necessary to avoid potentially harmful interactions.

Role of Vitamin D in Prevention of Falls and Fractures

The effect of vitamin D on risk of falls and fracture is under debate. Studies and analyses have reported effects that range from 20% reduction at a dose of 700-1000 IUs/day, to no effect at all, to an actual increase in falls and fractures with high-dose supplementation of 500,000 IUs/year.[33, 34, 35]  On the positive side, a meta-analysis of 12 randomized placebo-controlled clinical trials observed 20% lower risk of hip and nonvertebral fractures among individuals aged 65 and older who were supplemented with 700-800 IU/day vitamin D. The effect was dose dependent and not found at lower vitamin D dosages (400 IU or lower).[36, 37] On the negative side, several studies looking at high doses (100,000-500,000 IUs) in various settings found no effect or even a negative effect on falls and fractures.[38]Many questions remain to be answered regarding the impact of dose amount, dose timing, total number of doses, addition of calcium, and other issues.

HOW MUCH VITAMIN D IS NEEDED AND HOW TO GET IT

The goal of vitamin D supplementation is to achieve and maintain serum 25(OH)D levels in the healthy range. What constitutes an adequate serum 25(OH)D level? The IOM report concluded that, based on current data from randomized controlled clinical trials, people with less than 12 ng/mL are at risk for deficiency, 12-20 ng/mL are at risk for inadequacy, ≥20 ng/mL have adequate circulating levels, while those with levels >100 ng/mL are at risk for adverse effects.[1]

Many vitamin D clinical investigators and specialty societies such as the National Osteoporosis Foundation and the Endocrine Society recommend using the cut point of 30 ng/mL to denote sufficient serum 25(OH)D. In support of this designation is data indicating that intestinal absorption of calcium is maximized above 32 ng/mL and parathyroid hormone (PTH) concentrations in adults are their lowest at between 30 and 40 ng/mL 25(OH)D.2,6, [2, 6, 39, 40, 41

Figure 3. This illustration shows the continuum of 25(OH)D levels with area of controversy indicated in shading.

The IOM’s guidelines for vitamin D intake are based on what healthy individuals need to take in daily to maintain serum 25(OH)D in the healthy range (>20 ng/ml). These guidelines, or dietary reference intakes (DRIs), are a set of reference values for vitamins, minerals, and other nutrients used for dietary planning and assessment. DRIs are specific to age group, gender, and, for women, reproductive status.

Vitamin D supplements are available in over-the-counter tablets, liquids, and capsules in doses ranging from 200-5000 (D2/D3) and 50,000 IUs (D3). Prescription dosages of 50,000 and 8000 IU/mL injectable are available for physician use. High doses such as these are used under medical supervision to elevate serum 25(OH)D to healthy levels over weeks or months. Once an optimal serum level has been achieved, they are followed by lower doses usually taken daily or weekly for maintenance.

Current DRIs for Vitamin D

DRIs are based on data for the following:

In its 2010 report, the IOM revised its recommendations for vitamin D based on new research. The new recommendation for daily intake of vitamin D tripled the value previously considered adequate for children and adults from 200 IU to 600 IU/day.[8]

Current RDAs & AIs for Vitamin D

The following RDAs were established for children, teenagers, and adults by the recent IOM report:

The following AIs were established for infants (RDAs have not been developed for children under 1 year):

Assessing Vitamin D Status

Approximating a patient’s vitamin D status from their reported dietary and supplement intake can yield unreliable results. Such estimates are confounded by sun exposure or lack thereof, intestinal absorption irregularities, vitamin D and 25(OH)D sequestration in body fat (in obese patients), and other factors. As a result, serum 25(OH)D level is the best clinical tool available to provide a picture of a given patient’s vitamin D status.

Vitamin D status is assessed by measuring circulating calcidiol, 25(OH)D. Calcidiol is preferred over calcitriol because of its relatively long and stable concentration in the blood. Calcitriol has a much shorter half-life than calcidiol (15 hours vs. 15 days) and is closely regulated by calcium, phosphorus, and parathyroid hormone. Assays for measurement of serum calcidiol have been criticized by the IOM and others for lack of consistency and standardization. This has led many specialists to err on the side of caution and assume a slightly higher acceptable serum 25(OH)D levels.

How Much Is too Much?

No one can get too much vitamin D from sun exposure; however, one may have excessive 25(OH)D levels from supplemental intake. Excessive levels of vitamin D over an extended period can lead to hypercalcemia, excessively high levels of calcium in the blood. Symptoms range from mild (headaches, weight loss, increased urination) to severe (kidney stones, cardiac arrhythmia). Because increased vitamin D leads to higher serum calcium levels, prolonged exposure to doses over safe limits can lead to vascular and tissue calcification with damage to heart, vessels, and kidneys. Persistent blood levels of >200 ng/mL are considered toxic and potentially dangerous.[1] Fortunately the body regulates conversion of 25(OH)D to 1,25(OH)2D, the very potent biologically active form of the vitamin. This is why very high serum levels of 25(OH)D are necessary to cause toxicity.

IOM 2010 Daily Vitamin D Tolerable Upper Intake Level

0-6 months: 1000 IU (25 mcg)
7-12 months: 1500 IU (38 mcg)
1-3 years: 2500 IU (63 mcg)
4-8 years: 3000 IU (75 mcg)
≥9 years, including pregnant & lactating women: 4000 IU (100 mcg)

These tolerable upper limits are meant as guidelines. The serum level of 25(OH)D is what determines toxicity in a given individual. Even at well below toxic levels, serum levels of vitamin D chronically above the healthy range may have adverse consequences. For example, although inconclusive, observational data from one small study suggested that high-normal vitamin D levels (≥40 ng/mL or ≥100 nmol/L) may be associated with increased risk of pancreatic cancer in male smokers.[43]

Ensuring Vitamin D Sufficiency

How does the clinician determine the appropriate replacement and maintenance dose of vitamin D for a patient who is vitamin D deficient? IOM recommendations are based on what it takes to maintain adequate 25(OH)D levels in a population of healthy people, not persons with bone disease. In the elderly, infirm, or chronically ill, these recommendations may not apply. In such instances, vitamin D supplementation must be overseen on a case by case basis to ensure that healthy serum 25(OH)D levels are reached and held steady over the long term. This means experimenting with dose and following up with serum measurement at regular intervals.

It may be difficult to estimate the dose that will be most effective for a specific patient. Serum response to supplementation is nonlinear, with greater proportional impact at low serum levels than at high. Data from NHANES III were used to calculate the daily intake required to ensure that 97.5% of women over age 60 have 25(OH)D values at or above desirable level (30 ng/mL). The estimate: ≈2600 IUs of vitamin D per day. [44, 45] This is far above IOM-recommended intake levels, but well below the tolerable UL and could easily be accomplished through oral supplementation.

Research is indicating that the conditions under which vitamin D supplements are taken influence its vitamin D absorption. To maximize absorption, supplements should be taken with their biggest meal of the day[50]. Current data suggest that this may result in about a 50% increase in serum levels of 25(OH)D levels achieved.[46]  Compliance with daily supplementation schemes is consistently low (about 50%) in reported studies. As a result, weekly, monthly, or possibly  quarterly dosing may produce better outcomes, although there is less data showing a benefit to fall and fracture prevention using less frequent dosing.

Figure 3. Estimated additional vitamin D intake (up to 1886 IU/day) needed to correct vitamin D inadequacy.

NONSKELETAL EFFECTS OF VITAMIN D

Over the past decade multiple large prospective studies have observed extra-skeletal benefits of vitamin D. Correlations have been reported between high intake of vitamin D and lower rates of chronic diseases such as colon, prostate, breast and several other cancers, multiple sclerosis, rheumatoid arthritis, and type 1 diabetes, as well as a lower mortality rate.[40-50] Because these data came from observational studies, they were not included in the IOM’s analysis of vitamin D benefit, which restricted its analysis of vitamin D benefits to those pertaining to the skeleton. Further research is needed to clarify the full spectrum of benefits and risks associated with vitamin D.

 

CASE 1: EIGHTY-YEAR OLD MAN WITH VERTEBRAL FRACTURE

The first patient we will discuss is an 80-year-old retired teacher who has developed a spinal fracture while bowling. He reports having severe pain in his back despite analgesics. A review of his medical history shows a decline of 4″ in height since it was last measured (3 years). The patient reports having lost about 20 pounds in that same time period. He had gall bladder cancer 25 years ago, underwent chemotherapy and is currently in remission.

The patient is asked about his diet and activities.

He reports having very little outdoor activity since his fracture due to pain. Since that time, he walks very little at home and cannot walk his golf course. He routinely uses a wheelchair for mobility.

The patient reports that he doesn’t have much of an appetite and avoids dairy, fish, and fatty foods because they make him feel queasy and unwell.

Is this patient at risk of vitamin D deficiency?

His risk factors include his age, diet low in vitamin D, history of gall bladder disease (potential fat malabsorption), and lack of exposure to sunlight. It is likely that the patient is deficient in vitamin D, which may have contributed to low bone density and to his vertebral fracture.

The patient is referred for bone density measurement by DXA.

His spinal T-score is -5.0 and his hip T-score is -3.0.

Does this patient have primary osteoporosis?
It is not possible to make a diagnosis based on his T-score alone. T-scores are surrogate markers of bone strength and fracture risk that are based on aggregated data from postmenopausal Caucasian women over age 60.
In the 60+ female population, disease frequency is high and correlations between T-scores and fracture rates are reliable. In men, osteoporosis is far less prevalent. T-scores and even age-matched Z-scores are, therefore, less specific in men and don’t reflect fracture risk as reliably.

What other factors would help make a diagnosis of osteoporosis in this patient?
With a male patient, we have to dig deeper for evidence of elevated risk of fragility fracture. His history of fracture is one indicator of risk that we know about, probable lack of activity and diet low in calcium and vitamin D are two other likely risk factors. Running a series of lab tests can determine his levels of serum calcium phosphorus, alkaline phosphorus (biomarker of bone turnover), vitamin D, PTH, and urinary calcium excretion.

Lab results:

calcium 7.9 mg/dL (normal 8.5 - 10.9 mg/dL )
phosphorus 2.8 mg/dL (normal 2.4 - 4.1 mg/dL
bone-specific alkaline phosphatase 490 U/L (normal 20-140 IU/L)
25(OH) D 10 ng/mL normal (30 – 80 ng/mL)
PTH 300 pg/mL (normal 10 - 65 pg/mL)
urine calcium 23 mg/d (normal 100 - 300 mg/day)

What is the diagnosis?

Clearly, this patient is at risk for further fractures. His serum calcium is low and his 25(OH)D and urine calcium are very low. His PTH is quite high. When coupled with the patient’s low DXA T-score and history of fracture, alone sufficient to make a diagnosis of osteoporosis, these lab values point to vitamin D deficiency with secondary hyperparathyroidism.

What are the options for treatment?

Obviously, the patient’s vitamin D deficiency needs to be corrected. But first, the clinician looks for correctable secondary causes of his osteoporosis.
Are there “red flags” in the patient’s history?

Taken together, the history of weight loss and digestive discomfort strongly suggest the possibility of celiac disease.

The patient is tested for celiac disease

Results are positive for celiac disease. The patient is put on a gluten-free diet. He is referred to a dietician for counseling and education on maintaining a gluten-free lifestyle. The patient’s self-reported diet prior to diagnosis was low in dairy products and sources of vitamin D and calcium. It is common for patients with occult celiac disease to have lactose intolerance. In time, he may be able to eat dairy products without discomfort. In the meanwhile, lactose-free dairy products are available.

Only after the patient’s celiac disease is under control can his vitamin D (and calcium) status be addressed.
The patient is further worked up to rule out disorders associated with untreated celiac disease: diabetes, iron deficiency anemia, folate or B12 deficiency anemia, clotting abnormalities, colon cancer, thyroid malfunction, and GI malignancies.

The patient returns for follow-up after four months

When the patient returns, he reports that his GI symptoms are completely gone. With the patient’s celiac disease under control, the clinician can consider options for addressing his bone loss.

The patient is prescribed gluten-free calcium and vitamin D supplements

He is prescribed 1200 mg of supplemental calcium and 1800 IUs vitamin D daily. Special attention is placed on the type of supplement used to ensure that it is gluten free. Next, the physician discussed options for treatment of the patient’s bone loss. The clinician explains that the patient will not get the full benefit of any medication for bone loss unless his vitamin D deficiency is corrected. The patient’s calcium/vitamin D supplementation could be augmented with a bisphosphonate drugs. To ensure that he is on track, follow-up blood chemistry should be done after 3-4 months. If it doesn’t show an improvement, the patient could be switched to a quarterly or yearly prescription dose of vitamin D (e.g. 50,000 IU/month).

At the next appointment, the patient has bone specific chemistries run. His 25(OH)D is 56 ng/mL, PTH is normal, serum calcium is 9.3 mg/d, and biomarkers of bone turnover are down. Follow-up DXA shows an increase of 30%, moving in the right direction.

What further interventions should be made at this point?

The patient is instructed on principles of safe movement and started on physical therapy for improving posture, building muscle strength and improving balance to help him avoid falls and additional vertebral fractures in the course of daily activities.

 

CASE 2: 77- YEAR-OLD WOMAN IN NURSING HOME

The second case we will discuss is a 77-year-old woman who has resided in an assisted living complex for 5 years, since breaking a hip. The hip fracture was surgically repaired with no complications. The patient is 5′2″ and weighs 190 pounds. Since her hip fracture, the patient has used a walker. At the time of her fracture, she was prescribed daily oral alendronate for osteoporosis. She reports having discontinued it after a few months due to severe gastric upset, which resolved without medication thereafter. She has now been referred for bone loss evaluation and potential treatment.

What risk factors does this patient have for vitamin D deficiency?

The patient has several risk factors for vitamin D deficiency: her age, her lack of sun exposure, and her obesity. The patient is tested for levels of serum calcium phosphorus, alkaline phosphorus, vitamin D, PTH, and urinary calcium excretion.Her spine and hip DXA measurements show T-scores of -3 and -3.5 respectively.

Lab results:

serum calcium 6.5 mg/dL (normal 8.5 - 10.9 mg/dL )
phosphorus 2.8 mg/dL (normal 2.4 - 4.1 mg/dL
bone-specific alkaline phosphatase 490 U/L (normal 20-140 IU/L)
25(OH) D 8 ng/mL normal (30 – 80 ng/mL)
PTH 300 pg/mL (normal 10 - 65 pg/mL)
urine calcium 45 mg/d (normal 100 - 300 mg/day)

What impact could her 25(OH)D status have on osteoporosis therapy?

Optimal vitamin D repletion appears to be necessary to maximize response to antiresorptives in terms of BMD and antifracture efficacy.
In studies, vitamin D deficient and vitamin D replete subjects differed significantly for annualized spine and hip BMD changes adjusted for all available confounding factors (type of treatment, age, calcium intake, baseline BMD values, etc.).[51]

What treatment is recommended?

To start, a dietary assessment is made to estimate the patient’s current intake of calcium and vitamin D. Her self-reported diet is found to be low in vitamin D and calcium. She is counseled on sources of vitamin D and calcium that she can add to her diet. The patient reports that she has a hard time eating dairy products due to stomach upset. She is counseled to try lactose-free milk; however, her attitude suggests that she was unlikely to do so.
Next, the physician prescribes supplementation to bring the patient’s vitamin D level to the optimal range. Because the patient is obese, a higher dose of vitamin D will probably be required to raise her deficient circulating 25(OH)D level to the optimal range. The patient is prescribed 2000 IU/day vitamin D with 1000 mg calcium (in split doses).

To address the bone loss, the patient is prescribed monthly oral risedronate. It is hoped that monthly oral risedronate will not cause the GI issues experienced with oral alendronate.

What follow-up would be recommended?

The patient’s labs are rechecked in 4 months to assess her vitamin D and calcium status. She is tolerating the risedronate and her labs show improvement in 25(OH)D (30ng/mL), so her regimen is maintained, with a planned follow-up twice yearly.

The physician’s nurse then interviews the patient. She asks about the patient’s diet to assess her vitamin D and calcium intake. The patient reports that milk “disagrees” with her so she avoids dairy. She reports that she regularly eats eggs and bacon for breakfast, fried fish and chicken, and convenience foods for lunch and dinner. She doesn’t eat leafy greens and doesn’t like oily fish or other sources of vitamin D. In addition, the patient says that calcium tablets seem to be causing constipation. The nurse tells the patient that adding leafy greens to her diet and avoiding fried and processed foods will help with the constipation and tells her to keep eating the eggs, but reduce the bacon to weekends only. She instructs the patient to take her vitamin D supplement with breakfast to ensure absorption. On the topic of calcium, the nurse tells the patient that she may reduce her supplemental dose of calcium if she can get more calcium from her diet. Since dairy has given the patient trouble in the past, the nurse recommends that she try soy milk and fortified orange juice instead. They agree to check in a couple of months later at the patient’s next appointment with the physician to see how her diet is going.

Are there any other interventions recommended?

The patient is referred to a physiatrist, or rehabilitation medicine physician, to establish whether physical therapy is needed prior for safe in-house exercise classes in her assisted living complex. This examination reveals poor balance, very tight Achilles tendons at the ankles, and residual weakness in lifting and extending the hips, which could put her at increased risk of falling during daily activities or therapeutic exercise.
She is referred to a physical therapist for increased range of motion at the ankle, strengthening exercises of the hip, pelvis, and ankles, and high-level balance challenges. With completion of physical therapy, she was safe to begin exercise class in her assisted living facility.

The patient is encouraged to spend time outdoors and to improve her overall activity level in a supervised setting. She is referred to the in-house dietician for guidance on maintaining a low-calorie diet with the goal of maintaining vitamin D and calcium levels while attaining a healthy weight.

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Summary

Vitamin D plays a complex role in calcium homeostasis, PTH regulation, and promotion of overall health. Maintenance of serum 25(OH)D levels is critical to skeletal health and is influenced by multiple factors, endogenous and exogenous to the individual. There are many unanswered questions about the impact of vitamin D on skeletal health, fracture risk, and extraskeletal diseases. Additional research is needed to clarify the many unanswered questions about the full effects and function of vitamin D in human health.

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