Osteoporosis

Osteoporosis, which literally means "porous bone," is a disease of the skeleton in which the bones gradually lose density and begin to deteriorate. People with osteoporosis have brittle bones and an increased susceptibility to fractures of the hip, spine, and wrist. According to the National Institutes of Health (NIH), an estimated 10 million Americans have osteoporosis and 18 million more have low bone mass, placing them at an increased risk for the disease. Osteoporosis is common among the elderly, but the disease can strike at any age. Although eighty percent of those affected by osteoporosis are women, particularly menopausal and post-menopausal women, men are affected as well.

Osteoporosis is a potentially crippling disease. The latest estimates from the NIH indicate that osteoporosis is responsible for more than 1.5 million fractures annually, including 300,000 hip fractures, roughly 700,000 spinal fractures, 250,000 wrist fractures, and more than 300,000 fractures at other sites on the body. Fortunately, there are many medications and alternative therapies to help treat the condition. Medical experts agree, however, that most Americans can avoid osteoporosis altogether by eating well-balanced diet, exercising regularly, and living a healthy lifestyle.

Signs and Symptoms

Osteoporosis is sometimes considered a "silent disease" because bone loss can occur without symptoms. In fact, people may not know they have brittle bones unless a sudden strain, bump, or fall causes one of their bones to fracture or a vertebra (one of the 33 bony segments that form the spine) to collapse. Signs of a collapsed vertebra include:

• Back pain
• Loss of height
• Kyphosis—a spine deformity characterized by a hump back

Causes

Although many people think of the skeleton as an unchanging structure, bones are living growing tissues. Bone consists of a strong, flexible mesh of collagen fibers (proteins that form a soft framework) and calcium phosphate (a mineral that hardens the framework). Throughout a person's lifetime, new bone is added to the skeleton and old bone is removed (resorption). During the early years of life, new bone is added faster than old bone is removed. As a result, bones become larger, stronger, and more dense until they reach peak bone mass (maximum bone density and strength). Peak bone mass tends to occur between the ages of 30 and 35. After this age, however, the bones lose increasing amounts of protein and minerals—more than they can build up—and the bones become thin and porous. The same is true for menopausal women. During menopause, estrogen levels drop. Studies have shown that the female hormone helps protect against bone loss. Without the protective effects of estrogen, menopausal women are at an increased risk for developing osteoporosis.

Other than age and menopause, causes of osteoporosis can include:

• Long term use of certain medications, particularly steroids and thyroid medications (see Warnings and Precautions section)
• Cushing's syndrome (a condition caused by an excess of a steroid hormone called cortisol)
• Kidney failure
• Diseases of the thyroid or adrenal glands
• Deficiencies in calcium, vitamin D, vitamin A, vitamin K, and/or magnesium (it is important to note that very high intake of vitamin A may actually increase the risk of osteoporosis)
• Anorexia nervosa
• Hypogonadism (abnormally diminished function of the sexual organs, such as the testes in men)
• Elevated levels of prolactin (a hormone responsible for lactation)
• Alcoholism
• Rheumatoid arthritis
• Epilepsy
• Kidney failure
• Rare genetic disorders such as osteogenesis imperfecta, Ehlers-Danlos syndrome, and Marfan's syndrome
• Depression

Risk Factors

• Advanced age (50 years or older)
• Being of European or Asian ancestry
• Being female
• Living a sedentary lifestyle
• Being thin
• Anorexia nervosa
• Family history of osteoporosis
• Never having menstruated or given birth to a child
• Late onset of menstruation or early menopause
• Heavy caffeine use, smoking cigarettes and/or drinking alcohol regularly
• Low exposure to sunlight
• Diets low in calcium or high in sodium
• Diabetes
• Depression
• High exposure to heavy metals (such as cadmium, copper, and lead)
• Long-term use of certain medications including corticosteroids, antibiotics, drugs that suppress the immune system, and thyroid medications

Preventive Care

Osteoporosis is a highly preventable disease. As mentioned in the Causes section, osteoporosis develops when the amount of bone loss exceeds the amount of bone formation in the body. Although osteoporosis tends to occur in menopausal women and the elderly, the condition is most likely to develop in people who did not reach their optimal bone mass during their critical bone-building years (childhood and adolescence). Therefore, measures to prevent osteoporosis should begin during childhood and should last throughout adulthood into old age. Ensuring adequate intake of calcium, magnesium and vitamin D is vital. Weight-bearing exercise, such as walking and lifting weights, as well as other exercises, including tai chi, can also help stave off the disease. Research has shown that exercise early in life boosts bone mass, while exercise later in life helps to maintain bone mass. Exercise also increases strength, coordination and balance—important tools to help prevent falls that cause fractures, especially in the elderly. Other ways to help prevent falls include eliminating obstacles in the home such as throw rugs, loose cords, and low pieces of furniture, keeping rooms well-lit, using hip pads, and getting regular eye exams.

Diagnosis

If a healthcare practitioner believes that a person is at risk for osteoporosis, he or she often recommends a bone mineral density test (BMD) to determine whether an individual's bone mass is below, at, or above normal levels. BMDs are painless, noninvasive, and safe. They typically measure bone density in the spine, wrist, and/or hip (the most common sites of fractures due to osteoporosis), while others measure bone in the heel or hand. Having that information will help the healthcare practitioner determine a treatment approach. Prior to BMD tests, osteoporosis was only diagnosed after an individual suffered a bone fracture. Today, however, BMD tests allow physicians to identify people at risk for osteoporosis before a fracture occurs.

Treatment Approach

For those who are at risk for osteoporosis or already have the disease, current treatments are designed to boost bone mass and prevent (further) bone loss. For example, medications such as estrogen are commonly used to slow bone loss. Making lifestyle choices, such as consuming a diet rich in fruits and vegetables and participating in a weight-bearing exercise program can also enhance bone strength. Supplements such as calcium, vitamin D, isoflavones (ingredients found in soy products) and vitamin K, can help prevent osteoporosis and even slow the progression of the disease.

Lifestyle

Diet
Studies suggest that diets rich in the following foods and nutrients may help prevent bone loss in both men and women:

• Calcium
• Magnesium
• Potassium
• Fruits
• Vegetables

A large-scale study of older White women (a population at particular risk for osteoporosis) found that those who consumed diets higher in animal protein than vegetable protein experienced more bone loss and hip fractures than those who consumed greater amounts of vegetable protein. These results suggest that adding more vegetable protein and reducing the amount of animal protein may diminish bone loss and reduce the risk of hip fractures, but further studies are needed to confirm this hypothesis. Exercise
The main goal of exercise is to delay the onset of osteoporosis. This is best accomplished by regular exercise throughout life. Research has shown that exercise boosts bone mass early in life and prevents bone loss later in life. This continues to be true even during and following menopause. Exercise also improves balance, flexibility, strength, and coordination—thereby, reducing falls and fractures associated with osteoporosis. A combination of weight-bearing endurance activity (such as walking), strength-training (such as weight-lifting or yoga), flexibility and coordination exercises (such as tai chi) has been shown to prevent bone loss and boost muscle mass and bone density in people with osteoporosis.

Medications

Currently, estrogens, alendronate, risedronate, and raloxifene are approved by the U.S. Food and Drug Administration (FDA) for the prevention and treatment of postmenopausal osteoporosis. Calcitonin is approved for treatment only.These medications, also known as anti-resorptive medications slow or stop bone loss.

• Estrogen—boosts bone density and reduces the risk of fracture by decreasing the amount of bone lost, enhancing the body's ability to absorb calcium, and diminishing the amount of calcium excreted in the urine. When taken alone, estrogen can increase a woman's risk for developing cancer in her uterine lining (endometrial cancer); so many healthcare practitioners prescribe the hormone progestin in combination with estrogen to reduce this risk. Some studies have suggested that estrogen therapy also increases a woman's risk for breast cancer, abnormal blood clotting, and gallbladder disease. For this reason, many practitioners advise using very low doses of estrogen.
• Alendronate and risedronate—both of these medications belong to a class of drugs known as bisphosphonates. These drugs have been shown to boost bone density, slow or stop bone loss, and reduce the risk of fractures. Side effects are uncommon but may include abdominal pain, heartburn, nausea, and irritation of the esophagus. These effects may be minimized by taking the medications first thing in the morning before eating anything else, with 8 oz. of water, and standing upright for at least 30 minutes before ingestion.
• Raloxifene—from a class of drugs called Selective Estrogen Receptor Modifiers (SERMS), this medication has estrogen-like effects on bone (prevents bone loss) but does not increase the risk for breast cancer. Side effects can include hot flashes and blood clotting.
• Calcitonin—although it does not improve bone density as effectively as estrogen or the bisphosphonates, calcitonin slows bone loss, reduces spinal fractures, and eases pain associated with bone fractures. Calcitonin is considered an alternative for women who cannot take estrogen or biphosphonates.
• Parathyroid hormone—used in low doses, this drug can jump start bone production and increase bone mass. It is often prescribed for women who have low levels of estrogen, people who take corticosteroids, or women who are undergoing fertility treatment with gonadotropin-releasing hormone analogue.
• Testosterone—used to treat hypogonadism in men and in combination with estrogen to treat hot flashes in menopausal women. The effectiveness and long-term safety for women, however, is not known. Discuss potential use with your physician.

Surgery and Other Procedures

Although any bone can be affected by osteoporosis, fractures of the hip and spine are most serious. Hip fractures may cause permanent disability or even death. They almost always require hospitalization and major reconstructive surgery. People with osteoporosis caused by hyperparathyroidism (a condition in which the parathyroid glands secrete excess hormones) may experience improved bone density from a surgical procedure that removes the parathyroid glands (parathyroidectomy). Other surgical procedures that help boost bone mass are currently under investigation.

Nutrition and Dietary Supplements

Eating fruits and vegetables and consuming adequate amounts of calcium and vitamin D are crucial in the prevention of osteoporosis. Keeping bones healthy throughout life depends on getting sufficient amounts of specific vitamins and minerals, including phosphorous, magnesium, boron, manganese, copper, zinc, folate, and vitamins B12, B6, C, and K. Avoiding sodium, alcohol, and caffeine will also enhance bone health.

Calcium An inadequate supply of calcium over the lifetime is thought to play a significant role in contributing to the development of osteoporosis. In fact, many studies have shown that low intakes of calcium are associated with low bone mass, rapid bone loss, and high fracture rates. According to the National Institutes of Health, many Americans consume less than half the amount of calcium recommended to build and maintain healthy bones. Recommended intakes of calcium for the prevention and/or treatment of osteoporosis are as follows:

• Children: 800 to 1200 mg/day
• Adolescent girls: 1200 to 1500 mg/day
• Premenopausal women (19 to 50 years old): 1000 mg/day
• Older adults (51 to 70 years old): 1200 to 1500 mg/day

(Recommended intake for older women is 1500 mg/day, except for those on estrogen, who need only 1000 mg/day.)

Good dietary sources of calcium include low fat dairy products (such as milk, yogurt, and cheese), dark green, leafy vegetables (such as broccoli, collard greens, and spinach), sardines and salmon, tofu, and almonds. Since most people have difficulty obtaining the recommended amounts of calcium from their diets alone, supplements are an effective addition. Because there are several different types of calcium and a variety of supplements available, your healthcare provider can help you choose the most appropriate supplement for you. Calcium citrate tends to be the most easily absorbed and digested form.

Vitamin D
Vitamin D plays a major role in calcium absorption (calcium must be absorbed into the bloodstream in order to have an effect on the body) and bone health. Vitamin D supplements and/or exposure to the sun (about 20 minutes a day), in combination with calcium, can help heal bone fractures and decrease the risk of future bone breaks. Recommended intakes of vitamin D for the prevention and/or treatment of osteoporosis are as follows:

• Older adults (51 to 70 years old): 400 IU/day; (71 years and older): 600 IU/day

During the winter, or in the case of a bone fracture, 800 IU/day may be required.

Isoflavones
Isoflavones are substances that have estrogen-like effects on the body. Found primarily in soy products, isoflavones have been shown to increase bone density and slow bone loss in menopausal women. Results from several studies suggest that, in the years leading up to menopause, women may decrease their risk of osteoporosis by consuming soy products rich in isoflavones. Further studies are needed to confirm these findings, however.

Ipriflavone
Ipriflavone, a synthetic isoflavone derived from natural isoflavones found in soy, red clover, and other food sources, may also be effective in preventing and treating osteoporosis. Although several studies have found that ipriflavone prevents bone loss and increases bone density in menopausal women, other large-scale studies have failed to support these findings. Results from one study suggest that ipriflavone may even cause lymphocytopenia, a condition characterized by abnormally low white blood cell count. Further studies are needed to determine whether ipriflavone is safe and effective for the treatment and/or prevention of osteoporosis.

Essential Fatty Acids
A deficiency in essential fatty acids (such as gamma-linolenic acid [GLA], found in evening primrose oil, and eicosapentaenoic acid [EPA], found in fish oil) can lead to severe bone loss and osteoporosis. Studies have shown that supplements containing essential fatty acids help maintain or increase bone mass. Essential fatty acids have also been shown to enhance calcium absorption, increase calcium deposits in bones, diminish calcium loss in urine, improve bone strength, and enhance bone growth. Foods rich in essential fatty acids (including coldwater fish such as salmon and mackerel) may confer the same benefits.

Vitamin K
Studies show that women who consume vitamin K supplements may improve bone density and decrease their risk of bone fractures. The current recommended daily intake of vitamin K for adults is 75 to 120 mcg, but some researchers suggest that higher dosages may be necessary for optimal bone health. Be sure to consult with your healthcare provider to determine the most appropriate dosage for you. People taking blood-thinning medications such as warfarin should avoid vitamin K.

Preliminary studies also suggest that the following nutrients show promise in the prevention and/or treatment of osteoporosis:

• Zinc—stimulates bone formation and inhibits bone loss in animals
• Vitamin C—may limit bone loss in early years of menopause but results are inconclusive
• Fluoride—increases bone mineral density but may increase risk of fractures
• Dehydroepiandrosterone (DHEA)—available in supplement and cream form; studies have shown that cream applied to the inner thigh may boost bone density in older women
• Melatonin—loss of melatonin with age may contribute to development of osteoporosis, but further studies are needed to determine whether it helps to prevent or treat osteoporosis

See the Warnings and Precautions section for a list of supplements that should be avoided by people with osteoporosis.

Herbs

Although most herbs have not been studied extensively for the treatment of osteoporosis, many professional herbalists would recommend the following botanical remedies for the prevention and/or treatment of osteoporosis (particularly in postmenopausal women) because they have a proven track record for balancing hormones and benefiting bone health:

• Black cohosh (Cimicifuga racemosa)—contains phytoestrogens (estrogen-like substances that help protect against bone loss); has been shown to relieve menopausal symptoms; used traditionally by Native Americans for musculoskeletal disorders
• Chaste tree (Vitex agnus castus)—used traditionally for menstrual and menopausal symptoms; may prove to have benefits for preventing or treating osteoporosis as well
• Red clover (Trifolium pratense)—isoflavones extracted from this herb may slow bone loss in women, but it is not clear whether the whole herb has similar effects
• Wild yam (Dioscorea villosa)—may be beneficial for menopausal symptoms and osteoporosis but further studies are needed
• Horsetail (Equisetum arvense)—contains substances believed to strengthen bone
• Kelp (Fucus vesiculosus L.)—used for disorders of the male and female reproductive systems as well as for musculoskeletal disorders; rich in minerals so may be an effective complementary treatment for osteoporosis
• Oat straw (Avena sativa)—boosts hormone levels that stimulate cell growth

Chiropractic

Chiropractic manipulation should not be applied to areas of the body directly affected by osteoporosis. However, spinal manipulation and/or gentle chiropractic techniques may be safely provided to areas of the body that are not affected by osteoporosis. Because many people with osteoporosis are elderly, chiropractors are trained to modify their techniques to the bone density level of each individual.

Traditional Chinese Medicine

A TCM practitioner would generally treat osteoporosis with a combination of acupuncture and herbs. According to traditional Chinese beliefs, the kidney governs bone and stores the qi (energy) for bone and marrow. Osteoporosis occurs when the bone marrow is not longer nourished, and, according to TCM, this results from exhaustion of kidney Yin energy. The acupuncturist would energize the qi at points that stimulate kidney energy.

In addition to acupuncture, a Chinese practitioner would treat osteoporosis with a combination of herbs that boost estrogen levels and provide much-needed minerals for the skeleton. Several of these herbs overlap with remedies that might be chosen by a Western herbal specialist.

Estrogen-boosting herbs

• Black cohosh (Cimicifuga racemosa)
• Angelica (Angelic archangelica)
• Cypress (Cupressus sempervirens)
• Hops (Humuluis lupulus)
• Pomegranate husk (Punica granatum)
• Sage (Salvia officinalis)
• Ginseng (Asian ginseng)
• Licorice (Glycyrrhizia glabra)

Mineral-enhancing herbs

• Horsetail (Equisetum arvense)
• Stinging nettle (Urtica dioica)
• Knotweed (Polygunum aviculare)
• Hemp nettle (Galeopsis dubia or Gaelopsis ochroleuca)
• Maërl (Lithothamnium calcareum)

In addition to these herbs, the Chinese practices of qi gong and tai chi, as well as other types of exercise may enhance muscle tone and improve balance and coordination, thereby reducing the risk of falls (and subsequent bone fractures) associated with osteoporosis.

Other Considerations

Warnings and Precautions

Some studies suggest that excessive intake of vitamin A may increase the risk for osteoporisis. People with osteoporosis, or those at risk for it, should not exceed the daily recommended intake of vitamin A (900 mcg/day for men and 700 mcg/day for women) because high levels of this vitamin have been linked to decreased bone mineral density and an increased risk for hip fracture. The same is not true of carotenoids (a preformed version of vitamin A, such as beta-carotene). An appropriate balance of vitamin A—not to much and not too little—is necessary for normal bone development.

There are also certain medications that may contribute to the development of osteoporosis. For example, the long-term use of glucocorticoids (steroid hormones), thyroid medications, blood-thinners, diuretics (medications that promote excretion of urine), antibiotics, immune system suppressants, aluminum-containing antacids, and gonadotropin releasing hormone analogs (used to treat endometriosis) may cause bone loss. Use of these medications should be directed by your physician.

Prognosis and Complications

Bone fractures are the most common complications of osteoporosis and are a significant cause of crippling disability and death. After age 60, 25% of women have a spinal fracture—and that percentage doubles after age 75. By age 90, 33% of women and 17% of men have had a hip fracture, usually resulting from a minor fall or accident. Many elderly people who suffer a hip fracture lose the ability to walk, become housebound, require institutionalization, and, most significantly, up to 36% die within one year.

Although an estimated 1.5 million bone fractures in the U.S. each year result from osteoporosis, most of these fractures are preventable. Several medications are currently being researched that may expand the treatment options available to people with osteoporosis. With continued research, the future for osteoporosis prevention and treatment is promising. In the meantime, a combination of medications (particularly estrogen treatment), diet, exercise, and certain herbs and supplements can ease the pain associated with bone fractures and help slow the progression of the disease.

References

Adami S, Bufalino L, Cervetti R, et al. Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporosis Int. 1997;7:119-125.

Agnusdei D, Bufalino L. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int. 1997;61:S23-S27.

Agnusdei D, Crepaldi G, Isaia G, et al. A double-blind, placebo-controlled trial of ipriflavone for prevention of postmenopausal spinal bone loss. Calcif Tissue Int. 1997;61:142-147.

Alekel DL, St Germain A, Peterson CT, Hanson KB, Stewart JW, Toda T. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr. 2000;72:844-852.

Alexandersen P, Riis BJ, Christiansen C. Monofluorophosphate combined with hormone replacement therapy induces a synergistic effect on bone mass by dissociating bone formation and resorption in postmenopausal women: a randomized study. J Clin Endocrinol Metab. 1999;84(9):3013-3020.

Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis. JAMA. 2001;285:1482-1488.

Anderson JJB, Garner SC. Phytoestrogens and bone. Baillieres Clin Endocrinol Metab. 1998;12:53-557.

Atkinson C, Compston JE, Robins SP, Bingham SA. The effects of isoflavone phytoestrogens on bone; preliminary results from a large randomised controlled trial. Presented at: 82nd Annual Endocrine Society Meeting; June 23, 2000; Toronto, Ontario, Canada.

Atorvastatin. NMIHI. Accessed at http://www.nmihi.com/a/atorvastatin.html on January 2, 2018.

Baber R, Bligh PC, Fulcher G, Lieberman D, Nery L, Moreton T. The effect of an Isoflavone dietary supplement (P-081) on serum lipids, forearm bone density & endometrial thickness in post menopausal women [abstract]. Menopause. 1999;6:326.

Belkoff SM, Mathis JM, Fenton DC, Scribner RM, Reiley ME, Talmadge K. An ex vivo biomechanical evaluation of an inflatable bone tamp used in the treatment of compression fracture. Spine. 2001;26(2):151-156.

Blanch J, Pros A. Calcium as a treatment of osteoporosis. Drugs Today. 1999;35:631-639.

Blumenthal M, Goldberg A, Brinkmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Newton, Mass: Integrative Medicine Communications; 2000:201-204.

Brattstrom LE, Hultberg BL, Hardebo JE. Folic acid responsive postmenopausal homocysteinemia. Metabolism. 1985;34(11):1073-1077.

Bryant RJ, Cadogan J, Weaver CM. The new dietary reference intakes for calcium: implications for osteoporosis. J Am Coll Nutr. 1999;18:406S-412S.

Bunker VW. The role of nutrition in osteoporosis. Br J Biomed Sci. 1994;51(3):228-240.

Byers RJ, Hoyland JA, Braidman IP. Osteoporosis in men: a cellular endocrine perspective of an increasingly common clinical problem. J Endocrinol. 2001;168(3):353-362.

Can osteoporosis be prevented or avoided? American Academy of Family Physicians Accessed at https://familydoctor.org/ on October 27, 2018.

Chen YY, Hsue YT, Chang HH, Gee MJ. The association between postmenopausal osteoporosis and kidney-vacuity syndrome in traditional Chinese medicine. Am J Chin Med. 1999;27(1):25-35.

Clomiphene. NMIHI. Accessed at http://www.nmihi.com/c/clomiphene.html on January 2, 2018.

Consensus Opinion. The role of calcium in peri- and postmenopausal women: consensus opinion of the North American Menopause Society. Menopause. 2001;8:84-95.

Dalsky GP, Stocke KS, Ehsani AA, Slatopolsky E, Lee WC, Brige SJ Jr. Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women. Ann Intern Med. 1988;108(6):824-828.

Esomeprazole. NMIHI. Accessed at http://www.nmihi.com/e/esomeprazole.html on January 2, 2018.

Erdman JW, Stillman RJ, Boileau RA. Provocative relation between soy and bone maintenance. Am J Clin Nutr. 2000;72:679-680.

Fast facts on osteoporosis. MedicalNews. Accessed at https://www.medicalnewstoday.com/ on October 27, 2018.

Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999;69:74-79.

Gennari C, Agnusdei D, Crepaldi G, et al. Effect of ipriflavone—a synthetic derivative of natural isoflavones—on bone mass loss in the early years after menopause. Menopause. 1998;5:9-15.

Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass. Calcif Tissue Int. 1997;61:S19-S22.

Gillespie WJ, Avenell A, Henry DA, O'Connell DL, Robertson J. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis (Cochrane Review). In: The Cochrane Library, Issue 1, 2001. Oxford: Update Software.

Grados F, Depriester C, Cayrolle G, Hardy N, Deramond H, Fardellone P. Long-term observations of vertebral osteoporotic fractures treated by percutaneous vertebroplasty. Rheumatology (Oxford). 2000; 39(12):1410-1414.

Guillaume G. Postmenopausal osteoporosis and Chinese medicine. Am J Acupuncture. 1992;20:105-111.

Haguenauer D, Welch V, Shea B, Tugwell P, Wells G. Fluoride for treating postmenopausal osteoporosis (Cochrane Review). In: The Cochrane Library, Issue 1, 2001. Oxford: Update Software.

Haldeman S, Chapman-Smith D, Peterson DM. Guidelines for Chiropractic Quality Assurance and Practice Parameters: Proceedings of the Mercy Center Consensus Conference. Gaithersburg, Md: Aspen Publishers; 1993:174.

Heller HJ, Stewart A, Haynes S, Pak CYC. Pharmacokinetics of calcium absorption from two commercial calcium supplements. J Clin Pharmacol. 1999;39:1151-1154.

Kass-Annese B. Alternative therapies for menopause. Clin Obstet Gynecol. 2000;43(1):162-183.

Kelley G. Aerobic exercise and lumbar spine bone mineral density in postmenopausal women: a meta-analysis. J Am Geriatr Soc. 1998;46:143-152.

Krane SM, Holick MF. Metabolic bone disease. In: Fauci AS, Braunwald E, Isselbacher KJ, et al. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:2247:2258.

Kruger MC, Coetzer H, de Winter R, Gericke G, van Papendorp DH. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging Clin Exp Res. 1998;10:385-394.

Kruger MC, Horrobin DF. Calcium metabolism, osteoporosis and essential fatty acids: a review. Prog Lipid Res. 1997;36:131-151.

Labrie F, Diamond P, Cusan L, Gomez J-L, Belanger A, Candas B. Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. J Clin Endocrinol Metab. 1997;82:3498-3505.

LeBoff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA. 1999;281:1505-1511.

Leveille SG, LaCroix AZ, Koepsell TD, Beresford SA, Van Belle G, Buchner DM. Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA. J Epidemiol Community Health. 1997;51:479-485.

Mangione K, McCulley K, Gloviak A, et al. The effects of high-intensity and low-intensity cycle ergometry in older adults with knee osteoarthritis. J Gerontol A Biol Sci Med Sci. 1999;54A:M184-M190.

Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med. 1998;129:770-778.

Morselli B, Neuenschwander B, Perrelet R, Lippunter K. Osteoporosis diet [in German]. Ther Umsch. 2000;57(3):152-160.

Muhlbauer RC, Li F. Effect of vegetables on bone metabolism. Nature. 1999;401:343-344, 1999.

Nachtigall LE. Isoflavones in the management of menopause. Journal of the British Menopause Society. 2001;Supplement S1:8-12.

Nakaoka D, Sugimoto T, Kobayashi T, Yamaguchi T, Kibayashi A, Chihara K. Evaluation of changes in bone density and biochemical parameters after parathyroidectomy in primary hyperparathyroidism. Endocr J. 2000;47(3):231-237.

NIH Consensus Development Panel. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785-795.

Osteoporosis. NMIHI. Accessed at http://www.nmihi.com/n/osteoporosis.htm on October 27, 2018.

Osteoporosis. MedlinePlus. Accessed at https://medlineplus.gov/ on October 27, 2018.

Peacock M, Liu G, Carey M, McClintock R, Ambrosius W, Hui S, Johnston CC. Effect of calcium or 25OH Vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. J Clin Endocrinol Metab. 2000;85:3011-3019.

Peh WC, Gilula LA, Zeller D. Percutaneous vertebroplasty: a new technique for treatment of painful compression fractures. Mo Med. 2001;98(3):97-102.

Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr. 1998;68(suppl):1375S-1379S.

Roth JA, Kim B-G, Lin W-L, Cho M-I. Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem. 1999;274:22041-22047.

Ruml LA, Sakhee K, Peterson R, Adams-Huet B, Pak CYC. The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study. Am J Ther. 1999;6:303-311.

Ryan AS, Treuth MS, Elahi D. Resistive training maintains bone mineral density in postmenopausal women. Calcif Tissue Int. 1998;62:295-299.

Sakaguchi K, Morita I, Murota S. Eicosapentaenoic acid inhibits bone loss due to ovariectomy in rats. Prostaglandins Leukot Essent Fatty Acids. 1994;50:81-84.

Sakhaee K, Bhuket T, Adams-Huet B, Rao DS. Meta-analysis of calcium bioavailability: a comparison of calcium citrate with calcium carbonate. Am J Ther. 1999;6:313-321.

Scheiber MD, Rebar RW. Isoflavones and postmenopausal bone health: a viable alternative to estrogen therapy? Menopause. 1999;6:233-241.

Sellmeyer DE, Stone KL, Sebastian A, Cummings SR. A high ration of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Am J Clin Nutr. 2001;73:118-122.

Sharkey NA, Williams NI, Guerin JB. The role of exercise in the prevention and treatment of osteoporosis and osteoarthritis. Nursing Clin N Am. 2000;35:209-221.

Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000;15:515-521.

Somekawa Y, Chiguchi M, Ishibashi T, Aso T. Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women. Obstet Gynecol. 2001;97:109-115.

Snow-Harter C, Bouxsein ML, Lewis BT, Carter DR, Marcus R. Effects of resistance and endurance exercise on bone mineral status of young women: a randomized exercise intervention trial. J Bone Miner Res. 1992;7(7):761-769.

Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PWF, Kiel DP. Potassium, magnesium and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr. 1999;69:727-736.

Tyler V, Foster S. Tyler's Honest Herbal. Binghamton, NY: The Haworth Herbal Press; 2000.

Weber P. The role of vitamins in the prevention of osteoporosis—a brief status report. Int J Vitam Nutr Res. 1999;69:194-197.

What is osteoporosis? Cleveland Clinic. Accessed at https://my.clevelandclinic.org/ on October 27, 2018.

Yamaguchi M. Role of zinc in bone formation and bone resorption. J Trace Elem Exp Med. 1998;11:119-135.