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Vitamin K

A woman’s lifetime risk of fracturing her hip, vertebrae, or distal forearm is 40%.  An estimated 10 million Americans, 90% women, suffer from osteoporosis with an elevated risk of bone fractures with another 34 million having less severe bone thinning called osteopenia.  Osteoporosis can be prevent without medication.

Sadly, only a very few American women at risk for osteoporosis and fractures are being recommended preventive treatment.  Even among those experiencing osteoporotic fractures, half are not receiving any preventive treatment at all and virtually none adequate treatment.  In the U.S., 15% of women over 50 have osteoporosis and another 40% osteopenia.  Current recommendations are for all women to be screened for osteoporosis at age 65.  However, low-cost preventive strategies should be started when women are still in their 30's, if not earlier.

Symptoms of osteoporosis are a loss of height due to collapsing vertebrae, back pain from T5-L5 (mid to lower back), a Dowager's hump, or a fracture with minimal trauma.  Wrist fractures are especially suspicious.

Risk factors include age, family history, ethnic background other than sub-Saharan African, estrogen deficiency, tobacco use, steroid use, low calcium intake, physical inactivity, higher salt intake, heavy alcohol intake, and not being overweight. Certain medications, especially steroids, but also some anti-convulsants, HIV treatment, lithium, and thyroxine can increase osteoporosis.  Diseases including Crohn's disease, liver disease, rheumatoid arthritis, inflammatory bowel disease, lymphomas, multiple myeloma, thalassemia, acromegaly, amyloidosis, and leukemia all increase osteoporosis risk.

Bone mineral density is the primary component in bone strength, although the quality of the protein matrix is also important.  Both deteriorate with age.  Bone mineral density is most easily measured with a dual-energy x-ray absorptiometry of the spine and hip.  A T-score of 0.0 is the norm and that of healthy women ages 20-29.  A T-score of -1.0 is one standard deviation below normal or an 11% mineral loss. A Z-score is the number of standard deviations below the norm for the same age, sex, and ethnic background.  A T-score of less than -1.0 is osteopenia, and less than -2.5 osteoporosis.

Preventive strategies can avoid most cases of osteoporosis.  Obviously, stop smoking, avoid salt, avoid colas, and exercise daily.  Take an adequate doses of vitamin C (500 mg/day), vitamin D (800-1200 IU/day), calcium (for women only) (1000 mg/day), magnesium (250 mg once or twice a day), vitamin K(1) (500-1000 mcg/day), fruits and vegetables, vitamin B-12, and avoid excessive animal meatAvoid proton-pump inhibitors such as omeprazole, Prilosec, and Nexium since these can cause osteoporosis.  Opiates also increase fractures. These strategies not only help prevent and treat osteoporosis, they have many beneficial effects on other parts of the body.  Men should not take calcium due to its increasing prostate cancer and Parkinson's disease in men only. Thiazide blood pressure medication, by drawing out excess sodium, also reduces fractures.  Of all of these, vitamin K is the most important, since it helps build the bone protein matrix to hold the calcium in place.

While doctors most often use expensive medications such as risedronate (Actonel), raloxifene (Evista) and alendronate (Fosamax) for prevention, their $1,000 per year annual cost makes them extremely expensive for the limited benefits they give.  Actonel, Evista, and Fosamax should be reserved for the rare patient failing on the above strategies and suffering from a fracture.  Physicians rarely try the above low-cost alternatives and billions of dollars are being wasted every year using these high cost medicines for mild osteoporosis or in cases which would do just as well or better with the above low cost strategies.

Estrogen has largely been abandoned for post-menopausal women, but the use of very low dose estrogen (one half of a 0.625 mg tablet per day or very low dose patch) when combined with two weeks off estrogen every three-six months has been found helpful in preventing estrogen deficiency symptoms and is also quite good at preventing osteoporosis.  Some doctors suggest 14 days of a progestin every 6 months to prevent endometrial hyperplasia (B Ettinger et al. Ob Gyn 2001;98:205).  Current studies suggest that this low dose approach is probably safe, although traditional higher dose approaches have been found to have harmful health effects that outweigh the benefits.

Menostar low-dose estrogen patch is now being marketed for $48 per month.  It increases bone mineral density slightly more than calcium and vitamin D alone.  The results with Menostar look inferior to those with vitamin K, although the two have never been directly compared directly.

Bad: tobacco****, salt***, animal meat***, cola, polyunsaturated vegetable oil, vitamin A, and maybe low protein

Good: vitamin D*** or sunlight***, vitamin K-1***, vitamin B-12, calcium**, magnesium, potassium, fruits, vegetables, childbirth, weight-bearing exercise, higher vegetable protein, statins and possibly policosanol, estrogen, and maybe boron

Hip Fracture Review: Hip fracture is a devastating outcome associated with postmenopausal osteoporosis. This fracture causes considerable pain, disability, diminished quality of life, and mortality. Although bone loss is an important factor associated with hip fracture, there are other demographic and clinical factors such as those that increase the risk of falling (e.g., unsteady gait, medications) that contribute to the likelihood of experiencing a hip fracture. Nonpharmacological interventions to reduce hip fracture risk include regular weight-bearing exercise, fall intervention programs, and external hip protectors. Patients should receive calcium and/or vitamin D supplementation as necessary. Among available pharmacologic options, the bisphosphonates, risedronate (Actonel) and alendronate (Fosamax), have reduced the risk of hip fracture in postmenopausal women with osteoporosis. Raloxifene (Evista), salmon calcitonin nasal spray (Miacalcin), and teriparatide (Forteo) have not demonstrated hip fracture risk reduction in controlled clinical trials. Hormone therapy (HT) reduced hip fracture risk in a recent large placebo-controlled trial; however, the risk/benefit profile of HT has resulted in recommendations to consider alternatives for the management of osteoporosis. Postmenopausal women with osteoporosis should receive adequate calcium/vitamin D supplementation, be encouraged to exercise, and institute risk factor interventions. Treatment with a bisphosphonate should be considered for those who are also at increased risk for hip fracture. Hip fracture prevention in postmenopausal women. Kessel B. University of Hawaii, Obstet Gynecol Surv. 2004 Jun;59(6):446-55

Alcohol No Clear Benefit on Bones; Heavy Drinking Bad: 7,598 French women (mean age, 79.9 years) with bone mineral density tests found that compared with nonusers, women who drank 11-29 g of alcohol per day (1-2+ drinks) had higher bone mineral density values at the trochanteric site (p = 0.0017). Neither 1-10 g/day nor >30 g/day users had increased bone mineral density levels. These results were unrelated to estrogen replacement therapy use, dietary calcium intake, current smoking status, usual physical activity, educational attainment, household monthly income, and general health status. Alcohol intake was not associated with bone mineral density at the femoral neck. Total body bone mineral density was lower in subjects with alcohol intakes >30 g/day (p = 0.047). Effect of alcohol intake on bone mineral density in elderly women: The EPIDOS Study. Ganry O, Baudoin C, Fardellone P. Service d'Information Medicale et d'Epidemiologie, CHU Hopital Nord, Amiens, France. Am J Epidemiol. 2000 Apr 15;151(8):773-80

Alcohol No Help Hip Fractures Except Maybe Light Wine; Heavy Drinking Bad: In a prospective Danish study 17,868 men and 13,917 women from 1964-1992, a low to moderate weekly alcohol intake (1-27 drinks for men and 1-13 drinks for women) was not associated with hip fracture. Among men, the relative risk of hip fracture gradually increased for those who drank 28-41 drinks per week (relative risk (RR) = 1.75) and over 70 drinks RR = 5.28. Women who drank 14-27 drinks per week had an adjusted RR = 1.32. The risk of hip fracture differed according to the type of alcohol preferred: beer (RR = 1.46) wine 0.77 and spirits 0.82. Alcohol intake, beverage preference, and risk of hip fracture in men and women. Copenhagen Centre for Prospective Population Studies. Hoidrup S, Gronbaek M, Gottschau A, Lauritzen JB, Schroll M. Copenhagen University Hospital. Am J Epidemiol. 1999 Jun 1;149(11):993-1001. 

Boron Helped in Short Study: 3mg boron/d, an amount equal to intake on high fruit/veg diet markedly reduced calcium excretion and improved bone mineralization in 12 women on a metabolic unit in Grand Forks who had low 0.25mg/d intake before. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. Nielsen FH, Hunt CD, Mullen LM, Hunt JR.; Ed: 150 mcg in Sentury Vite senior multivit from WalMart.

Calcium, Tea Good; Late Menarche, Low Exercise & Low Sunlight Bad: A low BMI and milk consumption were significant risks only in the lowest 50% and 10% of the population, respectively. A late menarche, poor mental score, low BMI and physical activity, low exposure to sunlight, and a low consumption of calcium and tea remained independent risk factors after multivariate analysis, accounting for 70% of hip fractures. Excluding mental score and age at menarche (not potentially reversible), the attributable risk was 56%. Risk factors for hip fracture in European women: the MEDOS Study. Mediterranean Osteoporosis Study. Johnell O, Gullberg B, Kanis JA, Allander E, Elffors L, Dequeker J, Dilsen G, Gennari C, Lopes Vaz A, Lyritis G, et al. J Bone Miner Res. 1995 Nov;10(11):1802-15; But, In both men and women, the adjusted intakes of protein, saturated fatty acids, vitamin D, magnesium, and phosphorus were significantly higher in the high-calcium-intake group of 957 at UCSD. Am J Clin Nutr. 1991 Mar;53(3):741-4

Calcitonin SC Reduces Pain: In a 2 week DB PC study of 58 patients with osteoporosis with all on calcium 1000 mg/d, subcutaneously 100 IU salmon calcitonin increased beta-endorphin levels (p<0.001) with more pain relief (p<0.05). The effect of calcitonin on beta-endorphin levels in postmenopausal osteoporotic patients with back pain. Ofluoglu D, et al. Marmara University, Istanbul, Turkey. Clin Rheumatol 2006 Mar 31.

Celiac Disease May Cause 3-4% of Osteoporosis: In a study of 840 patients, researchers found osteoporosis victims have a much higher rate of celiac diase. 3-4% of osteoporosis victims had it due to celiac disease, an intestinal disease caused by an allergy to gluten, a wheat protein. The diarrheal type disease makes them unable to absorb normal amounts of calcium and vitamin D. William Stenson, Washington University, St. Louis. Treatment is a gluten-free diet. Arch Int Med 3/05

Childbirth Decreases Hip Fractures: Women who had never given birth were 44 percent more likely to break a hip during a 10-year period, starting when they were at least 65 years old. And the more children you have, the better, according to the report, published in the Journal of Bone and Mineral Research 4/25/03: among women who had experienced childbirth, with each additional birth, their risk of fracture dropped by nine percent. These findings may be helpful to women who have never given birth, lead author Dr. Teresa Hillier of Kaiser Permanente Northwest/Hawaii in Portland, Oregon.

Coffee, Obesity, Low Calcium OK: Large, prospective (n = 3068) women ages 47 to 56 with a follow-up of 3.6 years, 257 (8.4%) sustained a total of 295 fractures. After adjustment for covariates, the relative risk (RR) of sustaining a fracture was found to be 1.4 for a 1 standard deviation (SD) decrease in the spinal and femoral neck bone mineral density (BMD). previous fracture history increased risk of fracture [RR 1.7] and those reporting three or more chronic illnesses RR of 1.4, not using hormone replacement therapy (HRT) had a RR of 1.5 for all fracture types, smoking (RR 1.8). Weight, height, age, menopausal status, maternal hip fracture, use of alcohol, coffee consumption or dietary calcium intake were not independently associated. Finland, Risk factors for perimenopausal fractures: a prospective study. Huopio J, Kroger H, Honkanen R, Saarikoski S, Alhava E. Osteoporos Int. 2000;11(3):219-27

Cola Associated with Fractures?: A very small 126 teenager questionnaire study reports a strong association between cola beverage consumption and bone fractures in girls [the adjusted odds ratio (OR) = 3.59; p = 0.022]. High intake of dietary calcium was protective (adjusted OR = 0.284; p = 0.036). No association between the non-cola drinks and bone fractures was found. In boys, only total caloric intake was associated with the risk of bone fractures. Carbonated beverages, dietary calcium, the dietary calcium/phosphorus ratio, and bone fractures in girls and boys. Wyshak G, Frisch RE. J Adolesc Health. 1994 May;15(3):210-5; 

Colas Bad: A series of studies by Dr. Grace Wyshak at the Harvard School of Public Health has found about a fivefold higher rate of bone fractures among physically active teenagers who consume the most colas. NYT 9/17/00. High consumers of added sugars also had the lowest intake of the five food groups (grains, fruits, vegetables, protein foods and dairy products). Per capita consumption of sugars rose a whopping 28 percent in just 15 years, to 53 teaspoons a day by 1997 (all not actually eaten).

Cola Lowers Bone Mass: In the Framingham Offspring study of 2,820 adults, carbonated and noncola drinks made no difference in bone mass, but over 3 servings of cola per day lowed hip bone mass, possibly due to the phosphoric acid in colas. Tucker KL, Troy L, et al. Carbonated beverage consumption and bone mineral density. J Bone Miner Res. 2003;18(suppl 2):S241

Cola Lowers Bone Mass Again: A study looking at carbonated soft-drink consumption in 744 girls ages 12-15 found a significant inverse correlation was found between total carbonated soft-drink intake and bone mass of the heel in girls. McGartland C, Robson PJ, Murray L, et al. Carbonated soft drink consumption and bone mineral density in adolescence: The Northern Ireland Young Hearts Project. J Bone Miner Res. 2003;18:1563-1569.

Denosumab: Expensive Antibody Coming for Osteoporosis: Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. Monoclonal antibody denosumab binds RANKL and inhibits its action. In an industry-financed, random-assignment, open 12-month study of 412 postmenopausal women with low bone mineral density, patients received denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. Denosumab resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent vs. 4.6 percent with alendronate vs. -0.8 percent with placebo with similar changes elsewhere. Denosumab increased bone mineral density and decreased bone resorption. Denosumab in postmenopausal women with low bone mineral density. McClung MR, et al. Portland, Oreg. . N Eng J Med 2006 Feb 23;354(8):821-31. Ed: This appears to be a new, unnecessary and expensive drug for osteoporosis.  The vast majority of osteoporosis cases can be treated very effectively for $3 per month with vitamin K and vitamin D, which also have many other valuable benefits.

Estrogen Low Dose Helps with Minimal Side-Effects: DB PC study of Ultralow-dose micronized 17beta-estradiol in 167 women over 64yo for three years found 3% increases in bone marrow density to important bones at six months. No endometrial thickening.  Women with uteruses had two weeks of 100 mg/d of oral micronized progesterone every six months.  Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial. Prestwood KM, Kenny AM, Kleppinger A, Kulldorff M.

Estrogen: Low Dose Estrogen Patch Helps Osteoporosis: In a 2-year DB PC study of 417 women ages 60-80 with intact uteri and bone mineral density z scores of >-2.0, all received calcium and vitamin D supplementation.  Those also on unopposed transdermal estradiol at 0.014 mg/d had lumbar spine bone mineral density increased 2.6% vs. 0.6% for placebo (P <.001). Hip bone mineral density increased 0.4% for estradiol and decreased 0.8% for placebo (P <.001). Endometrial hyperplasia developed in 1 woman in the estradiol group but in none of the placebo group. Effects of ultralow-dose transdermal estradiol on bone mineral density: a randomized clinical trial. Ettinger B, Ensrud KE, Wallace R, Johnson KC, Cummings SR, Yankov V, Vittinghoff E, Grady D. Kaiser Permanente, Oakland, California. Obstet Gynecol. 2004 Sep;104(3):443-51

Exercise, if Light, No Value, But Vigorous is Good: Stewart, Kerry J., et al, "Fitness, fatness and activity as predictors of bone mineral density in older persons," Journal of Internal Medicine, Nov. 2002, Vol. 252, No. 5, pp. 1-8: 84 adults 55-75yo with HBP in study. Being overweight, especially abdominal obesity also increased bone density.

Folate and B-12 Reduce Hip Fractures in Stroke Victims: In a 2-year DB PC study of 628 Japanese stroke victims over age 64 with residual hemiplegia at least 1 year following first ischemic stroke, those taking 5 mg of folate and 1500 microg of mecobalamin had homocysteine levels decrease by 38% vs. increased by 31% with placebo (P<.001). The number of hip fractures per 1000 patient-years was 10 vs. 43 for placebo  (P<.001). One hip fracture was prevented for every 14 treated or roughly $2000 per hip fracture prevented by my calculations. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. Sato Y, Honda Y, et al. Tagawa, Japan. JAMA. 2005 Mar 2;293(9):1082-8.

Genetics: Osteoporosis is influenced by common variants (polymorphisms) of several different genes including those for the vitamin D receptor, estrogen receptor alpha, collagen type I alpha1, transforming growth factor beta-1 and some others are indicated to play a role in genetic determination of osteoporosis. Hubacek JA, Weichetova M. Prague. Cas Lek Cesk. 2005;144(1):5-9

Hydrochlorothiazide Preserves Bone Density: Large epidemiologic studies, including the Nurses’ Health Study, indicate that people treated with thiazide diuretics have higher bone mineral density (BMD) than those who don’t take them, and an approximately 30% lower risk of hip fracture. In a 3-year DB PC study of 320 healthy, normotensive men and women (aged 60 to 79) to hydrochlorothiazide, either 12.5 or 25 mg/day, led to gains in BMD at the hip of about 0.5% to 0.6% from baseline vs. a decrease of 0.3% for placebo. Spinal BMD was not significantly different. Ann Intern Med. 2000;133:516-26. 

Low Back Pain Patients Had Lower Vitamin D: In a study of 60 women with low back pain lasting more than 3 months compared to 20 matched healthy controls, patients with LBP had significantly lower vitamin D (25 OHD) levels (p < 0.05) and significantly higher parathyroid hormone (p < 0.05) and higher alkaline phosphatase (p < 0.001). Hypovitaminosis D (25 OHD < 40 ng/ml) was found in  81% of patients vs. 60% of controls, with an odds ratio of 2.97. Limited duration of sun exposure contributed 55% to the variance of vitamin D levels, limited areas of skin exposed 13%, and increased number of pregnancies 2% in patients. Despite the sunny climate, hypovitaminosis D is prevalent among Egyptian women in the childbearing period, especially those presenting with chronic LBP. The major determinant of hypovitaminosis D in our patients is limited sun exposure. Hypovitaminosis D in female patients with chronic low back pain. Lofti A, et al. Minia University , Cairo , Egypt , . Clinical Rheum 2007 Mar 22. Ed: Vitamin D 2000 units and vitamin K 1 mg or more may help low back pain.

Meat Protein May Worsen: Two contradictory studies came out in early 2001. an Amer J Clin Nutr study of 750 elderly women for 7 years found those with heaviest animal protein ratio vs. vegetable protein had 3.7 times as many fx and lost 0.8% of bone per year with vegetable group getting only 50% of protein from animal sources. Most women got only half the recommended calcium. A Harvard Framingham study of 600 senior men and women for 4 years found those getting the least protein lost 1% of bone vs. .25% for most protein diets. 12/00 J Bone & Mineral Research. The ratio of animal:vegetable did not differ between groups.

Meat Protein Worsens: High ratio of meat:vegetable protein was associated with an increase in bone fractures and bone loss, but not bone density in 1083 elderly women in prospective study. Am J Clin Nutr 01/01;118, UCSF

Magnesium, Alcohol, Fruits, Vegetables Increase Bone Mass: New SA, University of Surrey, higher intakes of magnesium, potassium, and alcohol were associated with higher total bone mass, or a positive link between fruit and vegetable consumption and bone health. Am J Clin Nutr 2000 Jan;71(1):142

Polyunsatured Vegetable Oil Not Good; Fruits and Vegetables Good: A 7-year follow-up of 891 Scottish women first studied at ages 45-55 found that higher intakes of calcium reduced femoral neck bone loss only modestly (r = 0.073, P < 0.05), similar to the other factors that follow. A modest amount of alcohol was associated with less lumbar spine bone loss. Greater femoral neck bone loss was associated with higher intakes of polyunsaturated fatty acids, monounsaturated fatty acids, retinol, and vitamin E with the latter 2 nutrients were highly correlated with polyunsaturated fatty acids. For premenopausal women, calcium and nutrients found in fruit and vegetables (vitamin C, magnesium, and potassium) were associated with femoral neck BMD. Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. Macdonald HM, New SA, Golden MH, Campbell MK, Reid DM. Am J Clin Nutr. 2004 Jan;79(1):155-165

Potassium Supplements Reduce Calcium Loss of High Sodium Diet: A Journal of Clinical Endocrinology and Metabolism May, 2002, study gave subjects a low 2 g. salt diet and measured the NTX protein level, a measure of bone breakdown. They then put subjects on a high 9 gram salt diet with a 3.5 g. potassium supplement or placebo. A 7% decrease in NXT occurred with the potassium vs. a 23% increase with placebo. Oranges, bananas, potatoes, spinach, and tomatoes as well as natural foods in general are high in potassium and low in sodium. UCSF Deb Sellmeyer. Potassium citrate is reported to increase bone density in post-menopausal females by 1% after 1 year by decreasing acids from foods such as dairy. R Krapf, Univ Basel, Switzerland. New Scientist 10/14/06.

Proton Pump Inhibitors Cause Osteoporosis: In a study of 149,000 British people over age 49, those taking high doses of PPIs for more than one year were 2.6 times as likely to bread a hip as those not taking any acid-blocker. Those on moderate doses for 1-4 years were 1.2 to 1.6 times as likely. Risk increased with duration of usage. Metz DC, et al. Univ Pennsylvania. JAMA 12/27/06 

Red Clover Helps Bone Density a Little: In a DB PC study of 205 women ages 49-65, red clover–derived isoflavone tablet (26 mg biochanin A, 16 mg formononetin, 1 mg genistein, and 0.5 mg daidzein) for one year resulted in significantly less lumbar spine bone mineral content and bone mineral density loss than those receiving placebo (P = .04 and P = .03). Treatment did not affect hip bone mineral content or bone mineral density, markers of bone resorption, or body composition. Cambridge Univ. Am J Clin Nutr. 2004;79:326-333. Ed: It's not worth it.

Salt, Protein Increase Bone Resorption: In a crossover study of 24 women who ate a high-protein, high salt diet for four weeks and the opposite for four weeks, the high diet caused more calcium loss in the urine.  It was concluded that the sodium- and protein-induced urinary Ca loss was compensated for by increased bone resorption and that this response may be influenced by vitamin D receptor genotype. Br J Nutr. 2004 Jan;91(1):41-51

Salt Linked Osteoporosis in Japan: 1658 adult females tested for sodium and calcium excretion and bone density. Urinary sodium and calcium excretion were found to be linked r=.438. Also found some evidence linking sodium intake and decreased bone mineralization. Clin Exp Pharm Physio 7/99;26:573

Salt increases calcium excretion: For every 100 mmol of sodium, 1 mmol of calcium is taken out of the body. Protein is another negative risk factor with 40-80 g/d increasing calcium excretion by 1 mmol. Ann NY Aca Sci 11/20/98

Salt exacerbates asthma, osteoporosis, renal disease, and carcinoma of the stomach: Am J Hypertens 5/97

Salt Harmful; Children Consumed Too Much: 8- to 13-year-old girls used nearly all the calcium in their diets unless their were heavy salt users in which case they excreted large amounts of calcium even if they did not consume sizable amounts of sodium. Ohio State. Child Mag 11/2000 p. 43. The U.S. government says only 225-500 mg/day of sodium is needed and a maximum limit of 2000 mg is recommended. However, boys average 3200 mg. of sodium per day and girls 2800 mg. or at least six times the maximum required. Even toddlers average 2600 mg.

Salt Avoidance Helps in DASH Diet: A 30-day study of 186 adults found a low salt diet reduced osteocalcin 10% and C-terminal telopeptide of type I collagen 17%. It reduced bone turnover and should increase bone density. The DASH diet and sodium reduction improve markers of bone turnover and calcium metabolism in adults. Lin PH, Ginty F, Appel LJ, Aickin M, Bohannon A, Garnero P, Barclay D, Svetkey LP. J Nutr. 2003 Oct;133(10):3130-6

Soy Protein No Help for Post-Menopausal Bones, Lipids, or Mental Functioning: In a DB PC study of 202 postmenopausal women given 25.6 g of soy protein containing 99 mg of isoflavones (52 mg genistein, 41 mg daidzein, and 6 mg glycetein or total milk protein as a powder on a daily basis for 12 months, cognitive function, bone mineral density, or plasma lipids did not differ significantly between the groups after a year. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. Kreijkamp-Kaspers S, Kok L, Grobbee DE, de Haan EH, Aleman A, Lampe JW, van der Schouw YT. University Medical Center Utrecht, The Netherlands. JAMA. 2004 Jul 7;292(1):65-74

Statins Help: Harvard research found increase bone density, 50% decrease in fractures, and less osteoporosis. June, 2000

Strontium Ranelate Reduces Osteoporosis Fractures: In a DB PC 3-year study of 5091 postmenopausal women with osteoporosis, those given strontium ranelate (2 g/day) had a reduction by 16% for all non-vertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031). Relative risk of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays. Strontium ranelate increased BMD throughout the study, reaching at 3 yr (P < 0.001): + 8.2% (femoral neck) and + 9.8% (total hip). Side-effects were similar in both groups. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis. Reginster JY, Seeman E, et al. University of Liege, Belgium and many other European centers. J Clin Endocrinol Metab. 2005 Feb 22. 

Teriparatide $$$$ for Osteoporosis: Recombinant first 34 amino acids of 94 aa parathyroid hormone. Daily SC injections for women who have already had fractures (the group most likely to benefit) cost $80,000 per vertebral and non-vertebral fracture prevented over 19 months of the study. 13% of women benefited with prevention of a fracture. (60% decrease vertebral and 40% decrease others, i.e. 14% to 5% and 10% to 6%). Therefore, 4,600 needlesticks to prevent a fracture as well. Some unreported number of fractures also prevented after the 19 months. Bisphosphonates only $63/mo vs. $516 for parathyroid hormone. Teriparatide may be better, but added cost per fracture prevented will be even higher if compared. Also, salt-avoidance may be better than either. Med Letter 2/3/03.

Teriparatide Injections Daily Helped Osteoporosis Back Pain: In a 14 DB PC study of 146 women with back pain due to osteoporosis with 30 months follow-up, women who daily self-injected teriparatide 40 microg did better than those on daily oral alendronate 10 mg with a 73% reduced risk for any back pain (relative risk 0.27) and 81% reduced risk of moderate or severe back pain (relative risk 0.19) vs. alendronate. Longterm reduction of back pain risk in women with osteoporosis treated with teriparatide compared with alendronate. Miller PD, et al. Lilly Research Laboratories, Indianapolis, Indiana, USA. J Rheumatol. 2005 Aug;32(8):1556-62. Ed: This is a highly expensive treatment, costing over $1000/month.  The results are good, but whether using all of my other recommended interventions for osteoporosis would change the results of this study, I don't know. Teriparatide stimulate new bone construction.

Trace Minerals Help: DB 2 year 59 woman study with 66 yos. Calcium 1000/day no better than Zn 15+Manganese 5mg+Copper 2.5mg/day although both were better than placebo and the author favors combo. J Nutr 1994 Jul;124(7):1060-4

Vitamin A: Fractures: Too Much Vitamin A Causes Hip Fractures: Women consuming 6660 IU/d had nearly double the hip fractures compared to the lowest intake of less than 1600 IU/d. Vitamin A is high in animal foods like milk and liver and supplements. JAMA 287:47, 2002

Vitamin S: Fractures: Too Much Vitamin A Causes Male Hip Fractures: 20 per cent of men with highest levels of blood vitamin A were 1.6 times more likely to break a bone and 2.5 times more likely to have a hip fracture than men with average levels. Another way of boosting vitamin A levels is to take beta-carotene, which the body then converts. But there was no link between blood levels of beta-carotene and fracture risk. Sweden. Analysed vitamin A levels in blood taken 30 years ago from more than 2300 men, who were then between 49 and 51 years old. NEJM 1/24/03.

Vitamin A: Fractures: Increased in Hip Fractures Due to Retinol: 18 year follow-up of 72,000 nurses found retinol 3000 units/day was associated with increases in fractures whether in food or pills. Beta-carotene was associated with a non-significant increase.

Vitamin B-12 Low in Osteoporosis: Vitamin B(12) is important to DNA synthesis. In a study of bone mineral density (BMD) and B-12 levels in 2576 adults, men with plasma B(12) less than 148 pM had significantly lower BMD at the hip, and women at the spine (p < 0.05). Low Plasma Vitamin B(12) Is Associated With Lower BMD: The Framingham Osteoporosis Study. Tucker KL, Hannan MT, et al. Tufts University. J Bone Miner Res. 2005 Jan;20(1):152-8. Ed: B-12 500 mcg every other day is on my list of recommended vitamins for adults over age 45.  It's very cheap.

Vitamin B-12 Linked to Vegan Teen Low Bone Density: In a study of 73 adolescents (9-15 y), macrobiotic diet until age 6 and then ovolactovegetarian, Blood B-12 levels were significantly lower (246 pmol/L vs. 469 pmol/L) and lower in the group with low BMD (p = 0.0035) or bone mineral content (BMC) (p = 0.0038) than in the group with normal BMD or BMC. When analyses were restricted to the group of formerly macrobiotic-fed adolescents, MMA concentration remained higher in the low BMD group compared to the normal BMD group. Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents. Dhonukshe-Rutten RA, Van Dusseldorp M, et al. Wageningen University, The Netherlands. Eur J Nutr. 2004 Aug 30

Vitamine C May Help: Not Vitamin A, Carotene, Vitamin E, or Selenium: In a study of 11,068 women ages 50-79 in the Women's Health Initiative Observational Study, vitamin A, retinol, beta-carotene, vitamin C, vitamin E, and selenium were estimated by using a self-reported food-frequency questionnaire and a random subset (n = 379) had serum levels of retinol, carotenoids, and tocopherols measured. After adjustment for important BMD-related covariates, only vitamin C (lower three-fourths compared with highest one-fourth) and use of hormone therapy (HT) (P < 0.01) were linked to higher bone density in the femoral neck, total-body (P < 0.045), spine (P = 0.03), and total-hip BMDs (P = 0.029). Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women's Health Initiative. Wolf RL, et al. Columbia University. . Am J Clin Nutr. 2005 Sep;82(3):581-8.

Vitamin D: Alfacalcidol Much Better than Vitamin D3: Due to strong feedback regulation, plain vitamin D is not activated in the kidney in vitamin-replete patients, while alfacalcidol, having been hydroxylated at position 1, bypasses regulation and increases available amounts of active D-hormone in different target tissues. In a 3-year DB study of 204 patients with established steroid-induced osteoporosis with or without vertebral fracture, those receiving 1 microg alfacalcidol plus 500 mg calcium per day had a 2.4% increase in lumbar spine bone mineral density vs. a -0.8% decrease for those on 1000 IU vitamin D3 plus 500 mg calcium (p < 0.0001) and a median increase at the femoral neck of 1.2% versus 0.8% (p < 0.006). The percentages with new vertebral fracture were 9.7% versus 24.8% (p = 0.005); and new nonvertebral fracture were 15% versus 25% (p = 0.081). The alfacalcidol group showed a substantially larger decrease in back pain than the plain vitamin D group (p < 0.0001). Only 3 patients in the alfacalcidol group and 2 patients in the vitamin D group had moderate hypercalcemia. Alfacalcidol versus plain vitamin D in the treatment of glucocorticoid/inflammation-induced osteoporosis. Ringe JD, et al. University of Cologne, Germany. . J Rheumatol Suppl. 2005 Sep;76:33-40.

Vitamin D: Sun Exposure Reduced Fractures in Elderly:  In a randomized study, Alzheimer's disease (AD) patients were assigned to regular sunlight exposure (n = 132) or sunlight deprivation (n = 132) and followed for 1 year. Serum 25-OHD level increased by 2.2-fold in the sunlight-exposed group. Eleven patients sustained fractures in the sunlight-deprived group, and three fractures occurred among the sunlight-exposed group (p = 0.0362; odds ratio = 3.7). BMD increased by 2.7% in the sunlight-exposed group and decreased by 5.6% in the sunlight-deprived group (p < 0.0001). Serum 25-OHD level increased from 24.0 to 52.2 nM in the sunlight-exposed group. Amelioration of osteoporosis and hypovitaminosis d by sunlight exposure in hospitalized, elderly women with Alzheimer's disease: a randomized controlled trial. Sato Y, et al. Tagawa, Japan. J Bone Miner Res. 2005 Aug;20(8):1327-33

Vitamin D: Almost All Elderly with Hip Fractures Had Very Low Vitamin D Levels: Of 82 adults (ages 52-97 with 63% age 80+) hospitalized with hip fractures, 50% reported using at least 400 IU per day of vitamin D through supplements and 13% of all patients were taking osteoporosis medication (3 estrogen, 5 alendronate, 1 etidronate, 1 raloxifene). The mean 25(OH)D concentration was 14.2. All but two of the 78 patients (97.4%) had 25(OH)D concentrations < 30 ng/mL and the majority (81%) of the patients had 25(OH)D concentrations < 20 ng/mL, including 21% < 9 ng/mL. Therefore, nearly all patients in this study hospitalized for fracture had vitamin D inadequacy, i.e., <80 ng/ml.  Prevalence of vitamin D inadequacy in a minimal trauma fracture population. Simonelli C, et al. HealthEast Osteoporosis Care, Woodbury, MN. Curr Med Res Opin. 2005 Jul;21(7):1069-74. Ed: It appears that adequate supplementation for the elderly is at least 2000 IU vitamin D. Vitamin K supplementation of 1 mg or more/day is also important. Sun exposure also helps.

Vitamin D 800 IU Helped: In a meta-analysis of double-blind RCTs of oral vitamin D supplementation (cholecalciferol, ergocalciferol) with or without calcium supplementation vs calcium supplementation or placebo in older persons (> or =60 years), five RCTs for hip fracture (n = 9294) and 7 RCTs for nonvertebral fracture risk (n = 9820) met inclusion criteria. All trials used cholecalciferol. A vitamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% and any nonvertebral fracture by 23%  vs calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons). Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. Bischoff-Ferrari HA, Willett WC, et al. Harvard. JAMA. 2005 May 11;293(18):2257-64.

Vitamin D at 800 IU and 2000 IU Didn't Help: In a 3 year DB PC study of 208 African American postmenopausal women, 20 microg/d (800 IU) of vitamin D(3) and 2000 IU for the third year with all women receiving calcium supplements of 1200 to 1500 mg/d led to no significant differences in BMD between the active and control groups throughout the study. There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss. There was an increase in BMD of the total body, hip, and radius at 1 year in both groups. Over the 3 years, BMD declined at these sites by 0.26% to 0.55% per year. A randomized controlled trial of vitamin D3 supplementation in African American women. Aloia JF, et al. Winthrop University Hospital, Mineola, NY. Arch Intern Med. 2005 Jul 25;165(14):1618-23

Vitamin D and Calcium Alone Didn't Helped: In a 25-month DB PC trial of 3314 elderly women over age 69 and living in community at risk for fractures, vitamin D 800 IU and calcium 1000 mg was of no benefit in reducing fractures. A literature review showed that any benefit is minor for falls or fractures. Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D-3) for prevention of fractures in primary care. Jill Porthouse et al. Univ. York, BMJ  2005; 330:1003 (30 April). Ed: This study was criticized by readers because the control group was told that they should get on vitamin D and calcium, and received the same every six month follow-up, but just not given free vitamin D and calcium.  The authors apparently did no check to see how many in the control group started their own vitamin D and calcium and did not measure vitamin D blood levels. I personally wrote in a response, which was published, complaining about the fact that vitamin K wasn't even mentioned.

Vitamin D Plus Calcium Helps Fracture Healing in Elderly: In a 12-week DB PC study of 30 elderly women average age 78 with humerus fractures, those receiving oral 800 IU vitamin D(3) plus 1 g calcium had a positive effect on fracture healing over the first 6 weeks. The Effect of Calcium and Vitamin D(3) Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study. Doetsch AM, Faber J, Lynnerup N, Watjen I, Bliddal H, Danneskiold-Samsoe B. Frederiksberg Hospital, Copenhagen, Denmark. Calcif Tissue Int. 2004 May 27

Vitamin D 100,000 IU Every 4 months Cuts Fractures: 2686 elderly ages 65-79 living in community participated in a 4.5 year DB PC study in England. Those on vitamin D had 20% fewer fractures (RR 0.78) overall and 30% fewer in typical osteoporosis sites (0.67) with 10% decrease in mortality as well (16.7% vs. 18.4%)(RR 0.88; p=.18). The dosage might still not been high enough since there was only a minor decrease parathyroid hormone. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. Daksha P Trivedi, Richard Doll, Kay Tee Kha. BMJ 2003;326:469. Chapuy reported that daily supplementation with vitamin D 800 IU and calcium reduced hip fractures by 30% over three years in 3,270 elderly women. Some studies with just vitamin D 400 IU/d not find benefit. 25-hydroxycalciferol has a half-life of 25 days. 

Vitamin D2 400,000 IU Annually Reduced Fractures: All women over age 64 in Health District 20 were eligible for a prospective community intervention study. A vial containing 400,000 IU of oral vitamin D2 was offered to all in the winters of 2000-2001 and 2001-2002. 45-47% of eligible women accepted the vitamin D: 50-55% of women ages 60-70 years and 22-26% of those ages > 90 years. Women who had received vitamin D, with respect to women who had not, decreased by 17% (p = 0.056) and 25% (p = 0.005) in the 1st and 2nd years. Those over age 75 were the most helped. 25-OH vitamin D concentrations rose by 9 ng/ml over 4 months after administration (p < 0.0001) in 120 checked. Effect of oral vitamin D2 yearly bolus on hip fracture risk in elderly women: a community primary prevention study. Rossini M, Alberti V, et al. Regione Veneto, Italy. Aging Clin Exp Res. 2004 Dec;16(6):432-6.

Vitamin D 400 IU with Calcium 500 Helps Deficient Women: DB PC 12 mo. 192 65+yos. Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency. Grados F, Brazier M, et al. Joint Bone Spine. 2003 Jun;70(3):203-8

Vitamin D 10,000 IU/wk No Benefit on 1000mg Calcium: In a 2-year DB PC study of women with an average age of 56, there was no statistically significant difference between those on calcium alone or calcium and vitamin D. Am J Clin Nutr. 2003 May;77(5):1324-9

Vitamin D Injection Most Cost Effective: It cost only $1500 per fracture prevent in Vitamin D injections for elderly females in nursing homes. Adding calcium increases cost per fracture prevented to $22,000. Cost-effectiveness of preventing hip fractures in the elderly population using vitamin D and calcium. Torgerson DJ, Kanis JA. QJM. 1995 Feb;88(2):135-9. Calcijex = calcitriol; paricalcitol (Zemplar)(D2); doxercalciferol (Hectorol)(D2)

Vitamin D and Calcium: Seasonal Bone Loss Reversed: In a random-assignment open study of 55 adults, half were given 500 IU oral vitamin D(3) and calcium 500 mg/day during the winter months. Before the supplement, both groups lost bone during the winter months. In the year of supplementation, the vitamin D group gained 0.3-0.9% lumbar and femoral bone while the control group continued to lose bone. Supplementation with oral vitamin d3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. Meier C, Woitge HW, et al. University Sydney.

Zinc Intake Linked with Both Increase and Decrease of Osteoporosis: The decrease: Am J Clin Nutr. 2004 Sep;80(3):715-21; The increase: Ann Nutr Metab. 2004;48(3):141-5; Zinc deficiency in growing rats may be associated with osteoporosis. J Trace Elem Med Biol. 1999 Jul;13(1-2):21-6; Plasma zinc levels did not differ between groups, but urinary zinc excretion was significantly higher in the women with postmenopausal osteoporosis (p = 0.002) due to bone resorption. Age Ageing. 1995 Jul;24(4):303-7.

Zinc, Manganese, and Copper Make Very Minor Difference: In a 2-year DB PC study of the effects of calcium supplementation (calcium citrate malate, 1000 mg elemental Ca/d) with and without the addition of zinc (15.0 mg/d), manganese (5.0 mg/d) and copper (2.5 mg/d) on spinal bone loss (L2-L4 vertebrae) in healthy older postmenopausal women (n = 59, mean age 66), changes in bone density were -3.53% (placebo), -1.89% (trace minerals only), -1.25% (calcium only) and 1.48% (calcium plus trace minerals). Bone loss relative to base-line value was significant (P = 0.0061) in the placebo group but not in the other groups. The only significant group difference occurred between the placebo group and the group receiving calcium plus trace minerals (P = 0.0099). Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. Strause L, Saltman P, et al. University of California at San Diego. J Nutr. 1994 Jul;124(7):1060-4. Ed: Granted this was a very small study, but it is the only study I have seen using a zinc supplement for osteoporosis, and the benefit of zinc was not apparent.

Thomas E. Radecki, M.D., J.D.