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serum levels are too low, and adequate calcium is not provided by the diet, calcium is taken from . : Clinical Updates Long-term dietary calcium deficiency is a known risk Osteoporosis Clinical Updates is a publication of the National factor for osteoporosis. The recommended daily cal- Osteoporosis Foundation (NOF). Use and reproduction of this publication for educational purposes is permitted and cium intake from diet and supplements combined is encouraged without permission, with proper citation. This 1000 mg/day for people aged 19 to 50 and 1200 mg/ publication may not be used for commercial gain. NOF is a day for people older than 50. For all ages, the tolerable non-profit, 501(c)(3) educational organization. Suggested upper limit is 2500 mg calcium per day. citation: National Osteoporosis Foundation. Osteoporosis Clinical Updates. Issue Title. Washington, DC; Year. Adequate calcium intake is necessary for attaining peak bone mass in early life (until about age 30) and for Please direct all inquiries to: National Osteoporosis slowing the rate of bone loss in later life.3 Although Foundation 1150 17th Street NW Washington, DC 20037, calcium alone (or with ) has not been shown USA Phone: 1 (202) 223-2226 to prevent -related bone loss, multiple stud- Fax: 1 (202) 223-1726 www.nof.org ies have found calcium consumption between 650 mg Statement of Educational Purpose and over 1400 mg/day reduces bone loss and increases Osteoporosis Clinical Updates is published to improve lumbar spine BMD.4-6 osteoporosis patient care by providing clinicians with state-of-the-art information and pragmatic strategies on How to take calcium supplements: prevention, diagnosis, and treatment that they may apply in ‡ Take calcium supplements with food. clinical practice. ‡ If unable to take calcium with food or if tak- ing acid-blocking medication, calcium citrate is Overall Objectives recommended Despite the availability of effective prevention, diagnostic, and treatment protocols for osteoporosis, research indicates ‡ Spread calcium out that it is significantly underdiagnosed and undertreated ‡ 600 mg or less is absorbed best at one time in the general population. Through this publication, NOF ‡ Best to take supplement at a relatively low- calcium encourages participants to incorporate current evidence meal and expert recommendations into clinical practice to ‡ Chew chewables, swallow tablets improve the bone health of their patients. ‡ Take with full glass of water and food Upon completion of each issue of Osteoporosis Clinical Dietary sources of calcium include: Updates, participants should be able to: ‡ Dairy products: milk (300 mg/cup), yogurt (300- ‡ Recognize current concepts in osteoporosis research 400 mg/cup) and cheeses (138 mg/cup skim cot- and clinical practice ‡ Identify implications of these concepts for osteoporosis tage cheese) patient care ‡ Fortified orange juices (300 mg/8 oz), breads (150- ‡ Adopt evidence-based strategies to study, prevent, and/ ® 200 mg/slice), and cereals (Total brand Raisin Bran or treat osteoporosis 1038 mg/cup); ‡ Improve patient care practices by integrating new data ‡ Nuts (almonds 75 mg/1 oz, about 25 nuts) and and/or techniques seeds (sesame seed butter, tahini, 64 mg/tbsp) Intended Audience ‡ Fish eaten with (sardines 325 mg/3oz, canned This continuing education activity is intended for salmon 183 mg/3oz) health professionals who care for patients at risk for or ‡ Soy milk (61 mg/cup) suffering from osteoporosis practicing in primary care, ‡ Tofu processed with calcium salts (164 mg/quarter endocrinology, geriatrics, gynecology, internal medicine, cup) obstetrics, orthopedics, osteopathy, pediatrics, physiatry, radiology, rheumatology, and/or physical therapy. ‡ Green vegetables, such as collards (357 mg/cup) This includes physicians, nurse practitioners, registered ‡ Beans, such as navy beans (126 mg/cup) and soy nurses, pharmacists, physician assistants, technologists, beans (261 mg/cup) researchers, public health professionals and health educators Calcium supplements are available in several forms: with an interest in osteoporosis and bone health. calcium carbonate (most common), calcium citrate,

3 and calcium phosphate. Compounds contain different Calcium Safety amounts of elemental calcium. Calcium intake should Concern has been raised about a possible connection be estimated on the basis of elemental calcium in the between calcium supplementation and cardiovascular supplement taken (shown on the nutrition supplement risks. Associations have been observed between calcium label). supplementation without vitamin D and increased risk Calcium in over-the-counter supplements is gener- of myocardial infarction (MI). Using a more powerful ally well absorbed in the various compounds available. tool of combining effects seen in individual studies by Individual users may find that one compound works meta-analysis of randomized trials of calcium supple- better for them because it causes fewer side effects, mentation (minus vitamin D), the same association was such as gas or constipation. Because the body doesn’t demonstrated: roughly a 30% increase in MI, but not readily absorb more than about 600 mg of elemental stroke or mortality.7,8 A similar, although smaller in- calcium at a time, it is best to take calcium supplements crease in MI was observed in meta-analysis of data from with a low-calcium meal and to spread out supple- the Women’s Health Initiative.9 ments, perhaps taking one in the morning and one at Data on calcium taken in conjunction with vitamin D night. Calcium carbonate is absorbed best when taken and pharmacotherapy for osteoporosis, however, have with food. Calcium citrate can be taken anytime. demonstrated no increase in overall mortality and Achieving bone-building and bone-preserving effects of cardiovascular events.10-12 There is still much that is pharmacologic therapies for osteoporosis requires ade- unknown about the risk of high calcium intake on the quate calcium intake. cardiovascular system. The current consensus is that calcium consumed through food intake is the best means to meet daily intake recommendations and is unlikely to have a nega- tive impact. Therefore, individuals should consume as much calcium as possible from foods. Supplements should be used only to bring all-source intake to rec- ommended levels of 1000-1200 mg/day. In general, more calcium than the recommended amount will not provide added benefit and may, indeed, pose a risk. In years past, the main concern about calcium supple- ments was lead contamination in calcium-carbonate based supplements derived from dolomite, bone meal, or unrefined oyster shell. Like other nutritional supple- ments, calcium supplements are not FDA tested for lead content. It is up to the manufacturer to ensure that a supplement meets FDA standards. The FDA Provisional Total Tolerable Intake level for lead is 75 mcg for adults. Several studies have found detectible lead in commercial calcium supplements.13,14 In 2008, the FDA tested lead content in 324 multivitamins sold in the U.S. Small amounts of lead were found in Figure 1. 7KLVFDOFLXPFDOFXODWRULVDYDLODEOHRQWKH12) most of them (320 of 324), but none came close to ZHEVLWH3DWLHQWVFDQXVHLWWRHVWLPDWHWKHLUFDOFLXPLQWDNH the harmful threshold (highest daily exposure was <5 DQGQHHGIRUVXSSOHPHQWDWLRQWRUHDFKLQWDNHJRDOV mcg/day).15 $YDLODEOHDWKWWSZZZQRIRUJDERXWRVWHRSRURVLV SUHYHQWLRQFDOFLXPFDOFXODWRU If the supplement has a USP label, the lead content has been tested and determined to be within accept- able levels. Most major brands of calcium supplements voluntarily meet the USP standards for purity and safe 4 lead levels. CME Program Eligibility Calcium is known to offset the effects of lead by block- Method of Participation in the Learning Process: Clinician ing its absorption (both in the supplement and in other learners will read and analyze the subject matter, conduct dietary contributors of lead).16,17 Research has shown additional informal research through related internet that blood lead levels are lower in peo ple who take searches on the subject matter, and complete a post-test 18 assessment of knowledge and skills gained as a result of the calcium supplements than in those who do not. Data activity. available to date support the view that patients are safe After participating in this activity, the reader has the taking calcium-plus-vitamin-D supplements from re- option of taking a post-test with a passing grade of 70% or spected manufacturers. Patients should, however, avoid better to qualify for continuing education credit for this supplements derived from dolomite, bone meal, or activity. It is estimated it will take 1.0 hour(s) to complete the reading and take the post-test. Continuing education unrefined oyster shell. Be advised that calcium carbon- credit will be available for two years from the date of ate preparations are currently the least expensive and publication. the most widely available. Alternatives to calcium car- bonate include calcium citrate, calcium phosphate, and Accreditation The National Osteoporosis Foundation is accredited by the (by prescription) calcium acetate. Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Vitamin D and Bone The National Osteoporosis Foundation designates this educational activity for a maximum of 1.0 AMA PRA Vitamin D regulates intestinal calcium absorption Category 1 Credit(s)TM. Physicians should only claim credit and helps mineralize bone. The most readily available commensurate with the extent of their participation in the source of vitamin D is direct sunlight, which some activity. people avoid because of skin cancer risk and concern The National Osteoporosis Foundation is accredited as a provider of continuing nursing education by the about wrinkles and photo damage. Additionally, the American Nurses Credentialing Center’s Commission on skin’s ability to metabo lize vitamin D declines with Accreditation. age. Other sources of vitamin D are needed such as fish The National Osteoporosis Foundation designates this liver oils, fatty fish, eggs, liver, and fortified foods such educational activity for a maximum of 1.0 continuing as milk and cereal. nursing education credit(s). Other healthcare providers will also be able to receive a Vitamin D deficiency can be a problem among certificate of completion; nurse practitioners and physician ™ individuals who avoid sunlight, do not drink vitamin assistants may request an AMA PRA Category 1 Credit(s) certificate of participation. D fortified milk, or do not take a multivitamin con- taining vitamin D. It is also common in people who Disclosure of Commercial Support are homebound or institutionalized, are on dialysis or It is the policy of the National Osteoporosis Foundation anticonvulsive medication, or who suffer from diabe- (NOF) to ensure balance, independence, objectivity, tes, hypertension, chronic neurological disorders, or and scientific rigor in all its sponsored publications and programs. NOF requires the disclosure of the existence of gastrointestinal diseases. In addition, research on hos- any significant financial interest or any other relationship pital inpatients found a significant degree of vitamin the sponsor, editorial board, or guest contributors have D deficiency (42%) in patients with no known risk with the manufacturer(s) of any commercial product(s) factors.19 discussed in an educational presentation. All authors and contributors to this continuing education activity have For a more in-depth coverage of the critical role of disclosed any real or apparent interest that may have direct vitamin D in calcium metabolism and maintenance of bearing on the subject matter of this program. bone health, please see the issue of Osteoporosis: Clinical NOF’s accreditation status with ACCME and ANCC does Updates entitled, “Vitamin D and Bone Health.” not imply endorsement by NOF, ACCME or ANCC of any commercial products displayed in conjunction with this US RDI for vitamin D is 600 IU for men and women activity or endorsement of any point of view. ages 50 to 70 and 800 IU for all people over age 70. The safe upper limit is 4000 IU. Dietary sources of vi- Statement Regarding Off-Label Use Any publication of the Osteoporosis Clinical Updates that tamin D include: discusses off-label use of any medications or devices will be ‡ Salmon 815 IU/half fillet

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retinol, the carotenoids have shown promise in studies to increase bone density and/or reduce fractures.26-30 In Support NOF ...... the Framingham study, the highest intake levels of total -RLQXVLQWKHÀJKWDJDLQVWRVWHRSRURVLV carotenoids were associated with reduced 15-year frac- ture incidence (46% in women and 34% in men).28 12)GHSHQGVRQWKHJHQHURVLW\RILQGLYLGXDOVZKR UHFRJQL]HRXULPSRUWDQWZRUNHGXFDWLQJWKHSXEOLF The recommended intake of vitamin A is 900 mcg/ DQGKHDOWKSURIHVVLRQDOVDOLNHRQKRZWRSUHYHQW day (3000 IU) for men and 700 mcg/day (2300 IU) for GLDJQRVHDQGWUHDWRVWHRSRURVLV women with a limit of 3000 mcg/day (10,000 IU).29 Dietary sources of vitamin A or its precursor carotene 7KHUHDUHPDQ\ZD\VWRVXSSRUW12)LQLWVPLVVLRQ include: WRGHIHDWRVWHRSRURVLV ‡ Skim or fat-free milk 500 IU/cup as retinol ‡ Beef liver 22175 IU/cup as retinol ,QGLYLGXDO*LYLQJ ‡ Carrot juice 45133 IU/cup as carotene

suming foods fortified with B12 or a supplement con- taining B .)38 effect, vitamin B sufficiency reduces fracture risk by 12 improving bone quality and/or preventing falls through collagen-mediated protection of neurologic function.37 Boron Whatever the exact process, further research is needed Currently no recommended daily intake or average 8

with chronic disease should be warned not to increases the need for calcium by interfering with cal- take magnesium supplements without first consulting cium absorption through increased secretion of para- their physician. thyroid hormone. Studies have also observed that phos- phorous deficiency may reduce the absorption of calci- The RDI for magnesium is 420 mg for men and 320 um and thereby lead to bone loss.65 The key is to main- mg for women. Dietary sources of magnesium include: tain a balance between intake of calcium and intake of ‡ Trail mix with chocolate chips, salted nuts, seeds phosphorus (roughly 2:1). The common Western diet 235 mg/cup is characterized by low calcium-to-phosphorus ratios ‡ Semisweet chocolate 193 mg/cup (less calcium than phosphorus). Research has demon- ‡ Spinach, canned, drained 163 mg/cup strated that habitually low calcium-to-phosphorus diets ‡ Beans, black, cooked, boiled, no salt,120 mg/cup negatively impact calcium metabolism.66 It seems clear Manganese, Copper, Zinc that adding dietary calcium and reducing non-nutritive phosphorus intake (i.e. soda drinks and foods high in The dietary minerals man ganese, copper, and zinc phosphorus preservatives) can be beneficial to bone are cofactors for enzymes required for healthy bone health. metabolism.62 The RDI for phosphorus is 700 mg/day for men and There is currently no recommended daily intake for women. Dietary sources of phosphorus include: manganese. Adequate intake for men is 2.3 mg/day and ‡ Cornmeal, self-rising enriched 860 mg/cup for women is 1.8 mg/day, with a tolerable upper limit ‡ Milk, canned sweetened, condensed 774 mg/cup of 11 mg/day. Dietary sources of manganese include ‡ Fast foods biscuit with egg and sausage 562 mg/ nuts, legumes, tea, and whole grains. Research in ani- biscuit mal models has suggested a potential role for manga- ‡ Fish, salmon, cooked, dry heat 491 mg/half fillet nese supplementation in maintenance of bone health; however, more research is needed.63,64 The recommended intake of copper for adults is 900 Strontium is a trace element found in seawater. Its mcg/day with an upper limit of 10000 mcg/day. primary source in the diet is seafood. Other strontium- Dietary sources of copper include organ meats, sea- containing foods include whole milk, wheat bran, food, nuts, seeds, cereals, whole grains, and cocoa. meat, poultry, and root vegetables. There are no rec- The recommended intake of zinc for adults is 11 mg/ ommended daily or adequate intakes established for day for men and 8 mg/day for women with an upper strontium. However, average daily intakes have been limit of 40 mg/day, assuming that the person has nor- estimated to be about 1–3 mg. mal kidney function. Dietary sources of zinc include Research on humans and animals over the past thirty- fortified cereals, eggs, dairy products, nuts, red meat, odd years has shown pharmacologic doses of strontium peas, and certain seafoods. Patients with chronic kidney to be associated with increased bone strength and re- disease should not take zinc supplements. duced fracture rates.67-71 Phosphorus Several large, randomized placebo-controlled studies of postmenopausal women with osteoporosis taking 1 to 2 The recommended intake for phosphorus is 700 mg/ grams/day of strontium in the form of the drug stron- day for men and women, with an upper limit of 4000 tium ranelate observed reductions in rates of fractures mg/day until age 70, after which the safe limit drops over 4 to 5 years: roughly 30% to 50% for vertebral to 3000 mg/day. Dietary sources of phosphorus in- fractures,15% to 20% for nonvertebral fractures, 20% clude dairy products, meat, peas, eggs, and some cere- to 30% for major fragility fractures, and 20% for hip als. Phosphorous is also widely used as a preservative fractures.72-74 (phosphoric acid) in carbonated beverages and pro- cessed foods. As is the case with many nutrients, too : much or too little phosphorus leads to problems. ? 50% Vertebral Fractures It has long been known that excess phosphorus intake ? 15-20% Nonvertebral Fractures 11

to be consumed or administered enterally under the discussion on vitamin A.) Supplements are widely supervision of a physician and which is intended for the available. specific dietary management of a disease or condition for which distinctive nutritional requirements, based Protein on recognized scientific principles, are established by There have been a large number of observational stud- medical evaluation.” 89 ies and clinical trials looking at the impact of protein In clinical trials, a medical food containing 27 mg ge- on bone.98–100 Although outcomes have varied, research nistein aglycone, 20 mg citrated zinc bisglycinate, and data support the view that adequate protein intake is 200 IU cholecalciferol (trade name FOSTEUM®) was needed to achieve peak bone mass in childhood and demonstrated to decrease markers of bone turnover maintain healthy bone in adulthood. In the elderly, nu- and increase markers of bone formation. While this trition is often inadequate, and protein intake may be trial did not report fracture outcomes and the magni- suboptimal for skeletal health. tude of change observed is very small in real terms, the A recent meta-analysis of hundreds of double-blind preliminary data are suggestive of bone density main- placebo-controlled clinical studies conducted over the tenance.90 Additional information is needed on fracture past 30 years found no association, negative or positive, outcomes and long-term impacts in order to establish between fracture rates and dietary protein (animal or if this intervention is a practicable adjunct and/or addi- vegetable) in healthy adults. The meta-analysis found tion to curent osteoporosis therapies. a small but significant positive correlation between Another under study is the coumestan-rich dietary protein intake and BMD, BMC (bone mineral red clover. Clover has been researched in recent years content), and markers of bone turnover at all skeletal in both animal and human studies.91,92 Typical of these sites. However, no reduction in fracture risk was ob- studies is the one-year double-blind trial reported by served.101 Because the studies under review did not Atkinson, et. al., that randomized postmenopausal include long-term interventional trials, the possibility women to placebo or a red-clover-derived isoflavone of positive effects on fracture rates over time could not supplement. Results showed significantly less spine be assessed. bone loss in the red-clover group along with higher Further investigation is needed to determine if changes markers of bone formation. No change was seen in to current protein intake recommendations are war- bone loss at the hip or markers of bone resorption.93 ranted for any specific age group. At present, daily Dietary sources of include soybeans, chick- intake at recommended levels from animal and/or veg- peas, red clover, and legumes. Long-term clinical trials etable sources is sound policy for patients of all ages. are needed to assess the effectiveness of isoflavones on Recommended intake of protein is 56 grams/day for fracture rates and BMD at various skeletal sites. adult men and 46 grams/day for adult women (roughly Omega-3, or n-3, polyunsaturated fatty acids come 1 gto 1.5 g/day per kg). Dietary sources of protein from plant sources (lignans) or animal sources (fish include: oil). Omega-3 fatty acids have been shown in animal ‡ Duck 51.89 g/half-duck and cell research to have a beneficial effect on bone ‡ Chicken meat 42.59 g/cup mass.94 However, these results have not been replicated ‡ Fish salmon, cooked dry heat 39.37 g/half-fillet to date in human studies. The effects of omega-3 fatty ‡ Fast food hamburger, double large patty 34.28 g/ acids on BMD have been variable, with either positive burger or no effect on BMD.95,96 Plant sources of omega-3 fatty acids (lignans) include Tea soybeans, flaxseed, and walnuts. Animal sources of Multiple population and retrospective studies have omega-3 fatty acids include fatty fish (e.g., salmon, investigated tea drinking and any effect it may have 97 mackerel, and sardines). Vegetable sources may be on bone and fracture risk. Observations have trended preferable to avoid any detrimental effects of retinol, in a slightly positive direction concerning BMD and found in high concentrations in fish oil. (See above fracture reduction.102–104 However, there have been no

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multivitamin con tains vitamin D (600 IU), she partici- vitamin A in multivitamins to the beta-carotene form. pates regularly in outdoor activities, and is not elderly, Animal and epidemiological studies have indicated that she is at low risk for low vitamin D. However, vitamin omega-3 fatty acids from nonretinol sources such as D deficiency is very common in American adults, espe- flax seed oil may have a positive impact on bone and cially African Americans. The only way to rule it out is cardiovascular health, so the physician recommends this to perform serum measurment. as an alternative source of omega-3 fatty acid.

What should be done to assess the patient’s bone Should the physician discourage continued use of health? supplemental magnesium, zinc, and soy? Because she is postmenopausal with a family history of Not if they are kept within safe limits (350 mg/day for fragility fracture, a baseline bone density scan is appro- magnesium and 40 mg/day for zinc). Because zinc and priate. The clinician prescribes a bone density test by magnesium are involved in healthy bone metabolism, DXA and schedules a follow-up appointment to discuss it is possible that intake of these minerals may be ben- results, future fracture risk (using the FRAX® tool) eficial to bone. However, research is lacking to support and, if warranted, possible pharmacologic options and this hypothesis. tracking of biochemical markers of bone turnover. The clinician recommends a varied diet that includes leafy greens, fruits, and vegetables. In addition, the cli- Case 2: 45-Year-Old Perimenopausal Woman nician recommends that the patient engage in weight- The second patient we will discuss is a 45-year-old bearing exercise and a bone density test at age 60. woman with no family history of osteoporosis. She is perimenopausal and concerned about maintaining her Case 3: 75-Year-Old Woman with Low Bone bone health. The clinician finds no indicators of elevat- Mass ed osteoporosis risk in her history. Neither she nor her The third patient we will discuss is a housebound el- parents has experienced bone fractures. derly woman, 75 years old, who lives alone. She is in She has always been in good health, has never smoked good general health. Her recent DXA scan is diagnostic or consumed alcohol, and has never taken medications of osteopenia (hip BMD –2.0). that cause bone loss. The clinician asks if the patient takes any supplements or herbal products, she reports What dietary supplements or nutriceutical that she takes mul tiple nutritional supplements, includ- SURGXFWVLIDQ\FRXOGEHRIEHQHÀWWRWKLVSDWLHQW·V ing multivitamins, flax seed oil, magnesium, zinc, and bone health? six fish oil capsules twice a day for their cardiovascular Adequate calcium, vitamin D, and protein intake have benefits. all been shown to significantly benefit bone health in elderly women. Although these alone will not prevent Does anything in the patient’s reported history osteoporosis, they are necessary components of an raise concern about her bone health? overall prevention or treatment plan. Perhaps. Observational studies suggest that ingestion Because of her age and lack of sun exposure, it is prob- of high doses of sup plemental retinol, found in high ably safe to assume that this patient is vitamin D de- concentrations in fish oil, may increase a woman’s risk ficient. Vitamin D deficiency contributes significantly of hip fracture. This patient’s daily fish oil intake may to bone loss. To establish serum calcium and 25-hy- reach the level of concern. droxyvitamin D levels, the physician orders appropriate blood panels. Should the patient be advised to curtail her use of ÀVKRLOVXSSOHPHQWV" The patient is asked about her diet. She reports that she It may be a good idea. The potential cardiovascular eats mostly canned soup, tea, and toast: foods she can benefit of fish oil supplements (for their omega-3 fatty easily prepare. acid content) may be offset by skeletal harm. The clini- cian recommends that the patient discontinue intake &DQWKHSDWLHQW·VGLHWEHPRGLÀHGWRLPSURYHKHU of fish oil supplements and that she limit her intake of bone status? 16 Her diet is high in sodium and low in calcium and pro- Res. 1998;13(2):168–74. 6 Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ. Effect of calcium tein. It is advisable for her to take a daily supplement supplementation on bone loss in postmenopausal women. N Engl J Med. that contains adequate vitamin D (800 IU) and calcium 1993;328(7):460–4. 7 Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older (1000 mg). The clinician explains the importance of ad- women receiving calcium supplementation: randomised controlled trial. equate protein, calcium, and vitamins and recommends BMJ. 2008;336:262 adding nuts, dairy foods, fresh fruits, and vegetables to 8 Bolland MJ, Avenell A, Baron JA, et. Al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. her diet. To help the patient make these dietary chang- 2010 Jul 29;341:c3691. es, the clinician makes an appointment with a dietician 9 Bolland MJ, Grey A, Avenell A, Gamble GD, IR. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis who can help her develop a healthy eating plan she can of the Women’s Health Initiative limited access dataset and meta-analysis. manage on her own. BMJ. 2011; 342:d2040. 10 Camm JA. Review of the cardiovascular safety of and other for the treatment of osteoporosis. Clin Ther. 2010;32:426– Are there any other measures that can be taken to 36. help this patient preserve her bone mass? 11 Christensen S, Mehnert F, Chapurlat RD, Baron JA, Sørensen HT. Oral bisphosphonates and risk of ischemic stroke: a case-control study. Oral Inactivity is an established risk factor for bone loss and bisphosphonates and risk of ischemic stroke: a case-control study. Osteopo- osteoporosis. The patient is referred to a physical thera- ros Int. 2011 Jun;22(6):1773–9. 12 LaCroix AZ, Kotchen J, Anderson G, et. al. Calcium plus vitamin D pist to develop a safe movement/exercise plan to ease supplementation and mortality in postmenopausal women: the Women’s the patient into bone-preserving weight-bearing exer- Health Initiative calcium-vitamin D randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2009 May;64(5):559–67. cises that she may perform at home. 13 Bourgoin BP, Evans DR, Cornett JR, Lingard SM, Quattrone AJ. Lead con- tent in 70 brands of dietary calcium supplements. Am J Public Health. 1993 The clinician discusses drugs approved for osteoporosis Aug;83(8):1155–1160. prevention and recommends that the patient consider 14 Scelfo GM, Flegal AR. Lead in calcium supplements. Environ Health Per- beginning drug therapy to prevent further bone loss. spect. 2000 Apr;108(4):309–313. 15 United States Department of Health & Human Services. U.S. Food and Drug Administration. Survey Data on Lead in Women’s and Children’s Vitamins. August 2008. Available at: http://www.fda.gov/Food/Food- SUMMARY Safety/FoodContaminantsAdulteration/Metals/Lead/ucm115941.htm. Accessed January 23, 2012. There are multiple effective FDA-approved thera- 16 Heaney RP. Lead in calcium supplements: cause for alarm or celebration? peutics for preventing and treating osteoporosis. JAMA. 2000;284:1432–3. Unfortunately, there are also hundreds of non-FDA-ap- 17 Gulson BL, Mizon KJ, Palmer JM, Korsch MJ, Taylor AJ. Contribution of lead from calcium supplements to blood lead. Environ Health Perspect. 2001 proved nutriceutical products on the market that claim Mar;109(3):283–8. to do the same things. Healthcare providers can edu- 18 Muldoon SB, Cauley JA, Kuller LH, Scott J, Rohay J. Lifestyle and so- ciodemographic factors as determinants of blood lead levels in elderly cate patients about which products’ claims can be sup- women. Am J Epidemiol. 1994;139:599–608. ported by data, which products may potentially benefit 19 Thomas MK, Lloyd-Jones DM, Thadhani RI, et. al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338(12):777–83. bones, and which provide no benefit and may indeed 20 Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E. Reti- cause harm. Through this process, patients become nol intake and bone mineral density in the.elderly: the Rancho Bernardo better able to make more-informed choices regarding Study. J Bone Miner Res. 2002 Aug;17(8):1349–58. 21 Binkley N, Krueger D. Hypervitaminosis A and bone. Nutr Rev. their healthcare options. 2000;58:138–144. 22 Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA. 2002;287:47–54. REFERENCES 23 Melhus H, Michaelsson K, Kindmark A, et. al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased 1 Institute of Medicine, Food and Nutrition Board. Dietary Reference risk for hip fracture. Ann Intern Med. 1998 Nov 15;129(10):770–8. Intakes for Calcium and Vitamin D. Washington, DC: National Academy 24 Caire-Juvera G, Ritenbaugh C, Wactawski-Wende J, Snetselaar LG, Chen Press, 2010. Z. Vitamin A and retinol intakes and the risk of fractures among partici- 2 United States Department of Agriculture. USDA National Nutrient Da- pants of the Women’s Health Initiative Observational Study. Am J Clin Nutr. tabase for Standard Reference. Release 24. Vitamin A, IU Content of Se- 2009 Jan;89(1):323–30. lected Foods per Common Measure. Available at: https://www.ars usda. 25 Lim LS, Harnack LJ, Lazovich D, Folsom AR. Vitamin A intake and the gov/SP2UserFiles/Place/12354500/Data/SR24/nutrlist/sr24a318.pdf. risk of hip fracture in postmenopausal women: the Iowa Women’s Health Accessed November 3, 2011. Study. Osteoporos Int. 2004 Jul;15(7):552–9. 3 Kanis JA. The use of calcium in the management of osteoporosis. 26 Barker ME, McCloskey E, Saha S, et. al. Serum retinoids and beta-caro- Bone.1999;24(4):279–90. tene as predictors of hip and other fractures in elderly women. J Bone Miner 4 Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ. Long-term effects Res. 2005 Jun;20(6):913–20. of calcium supplementation on bone loss and fractures in postmenopausal 27 Wattanapenpaiboon N, Lukito W, Wahlqvist ML, Strauss BJ. Dietary ca- women: A randomized controlled trial. Am J Med. 1995;98(4):331–5. intake as a predictor of bone mineral density. Asia Pac J Clin Nutr. 5 Riggs LB, O’Fallon MW, Muhs J, O’Connor MK, Kumar R, Melton JL. 2003;12(4):467–73. 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