What was NEW in 1999?
December 1999: Statins may increase bone formation
Mundy, G.(1999). Stimulation of bone formation in vitro and in rodents by statins [see comments]. Science 286(5446): 1946-9.
A very interesting report that statins may increase production of BMPs (bone morphogenic proteins) and thus enhance bone formation.
November 1999: Bone biochemical markers - statistical significance not the same as clinical utilityBauer, D. C.(1999). Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures. J Bone Miner Res 14(8): 1404-10.
Marcus, R.(1999). The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. J Bone Miner Res 14(9): 1583-95.
These two studies show that biochemical markers are significantly related to the change in bone mineral density, but the relationship is too weak to be useful for routine testing of individual patients. Check out the new page about markers.
October 1999: Osteoprotegerin
Yasuda, H.(1999). A novel molecular mechanism modulating osteoclast differentiation and function. Bone 25(1): 109-13.
Morony, S.(1999). A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1beta, TNF-alpha, PTH, PTHrP, and 1, 25(OH)2D3 . J Bone Miner Res 14(9): 1478-85.
This factor is so new that there is no agreement about it's name! It is a member of the TNF receptor family, and it blocks bone resorption. At the 1999 ASBMR meetings were reports of giving it to human volunteers, who showed a rapid reduction in the markers of bone resorption. In mice it increases bone density and blunts the effects of metastatic cancer to the bone. Read about remodelling and watch the movie about origination, which shows how osteoprotegerin and related factors work.
September 1999: Bisphosphonates inhibit the cholesterol pathway and HMG CoA reductase inhibitors reduce bone resorption
Benford, H. L.(1999). Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs. Mol Pharmacol 56(1): 131-40.
Bassa, B. V.(1999). Effect of inhibition of cholesterol synthetic pathway on the activation of Ras and MAP kinase in mesangial cells. Biochim Biophys Acta 1449(2): 137-49.
van beek, E.(1999). The role of geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants in vitro: A clue to the mechanism of action of nitrogen-containing bisphosphonates. J Bone Miner Res 14(5): 722-9.
Fisher, J. E.(1999). Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci U S A 96(1): 133-8.
Luckman, S. P.(1998). Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 13(4): 581-9.
Several papers this year have been published which all find that inhibition of the mevalonate pathway is one mechanism of action of the bisphosphonates. See the updated pages on bisphosphonates for more details.
August 1999: Vertebral bone density is same in men and women
Ebbesen, E. N.(1999). Age- and gender-related differences in vertebral bone mass, density, and strength [In Process Citation]. J Bone Miner Res 14(8): 1394-403.
In this study, the 3rd lumbar vertebral was measured to determine the size, the volumetric density (ash weight/volume) and the compressive stress. Men and women had similar values. Men, however, had bigger bones, so the total bone mineral and compressive load was greater. Also, interestingly, the bone density decreased with age by a factor of 2.6, whereas the strength decreased by a factor of 4. See page about male osteoporosis.
July 1999: Weight loss is accompanied by bone loss
Salamone, L. M. Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial. Am J Clin Nutr 1999; 70: 97-103
This study showed that women aged 44-50 in a clinical trial of healthy lifestyle who were assigned to the intervention group lost an average of 3.2kg, but they lost bone density twice as fast as those who were in the weight-stable control group. This goes along with other studies that link weight changes to bone density changes, described on the nutrition page.
June 1999: Lower dose estrogen prevents bone loss in women older than 65
Recker, R. R.(1999). The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial. Ann Intern Med 130(11): 897-904.
This study used a dose of premarin of .3mg/day, and the bone density was stable in these women. All were given adequate calcium and vitamin D. The authors did not test whether the higher dose would have a better effect. This study shows that a low dose is definitely better for the bone than no estrogen, and that calcium and vitamin D alone do not substitute for estrogen. Click to go to the estrogen page.
May 1999: Vitamins: We need more D and K, but watch out for A
Feskanich, D.(1999). Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 69(1): 74-9.
This report from the Nurses' Health Study showed that low vitamin K intake increased the risk of a hip fracture. Also, the risk of hip fracture was decreased with lettuce consumption (RR: 0.55) for one or more servings per day compared with one or fewer servings per week.
Melhus, H.(1998). Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 129(10): 770-8.
The study was from Sweden, where 247 women with hip fracture were compared with 873 matched controls. Every 1mg/day increase in vitamin A (retinol) intake increased the risk of hip fracture by 68%.
Women from Boston with hip fractures had lower vitamin D than control women. (LeBoff, MS,(1999). Occult Vitamin D deficiency in postmenopausal US women with acute hip fracutre. JAMA 281:1505.) Also, Compton, J wrote an editorial in the BMJ 1998;317:1466-1467 about vitamin D intakes. She concludes that vitamin D intakes should be increased to help prevent osteoporosis. A study last year showed a high incidence of low vitamin D in hospitalized patients in the United States. Thomas, M. K.(1998). Hypovitaminosis D in medical inpatients . N Engl J Med 338(12): 777-83.
The current recommended dose of vitamin D is probably too low, especially in people who live in northern countries. But most vitamin D supplements also contain high contents of vitamin A. Some are labelled "vitamin D" and don't list the vitamin A, but it is often there, especially if it comes from cod liver oil.
A patient of mine just discovered a brand of vitamin D that does not contain vitamin A. It is OPTIMUM brand vitamin D, in capsules of 400 IU each. The company which makes this (Magno-Humphries) states that "we are currently the only manufactures of a product of this nature in the Northwest (or Nation as far as we have found)." Click to read more about vitamin D on these web pages.
April 1999: Use of hormones in US women
Keating, N. L.(1999). Use of hormone replacement therapy by postmenopausal women in the United States. Ann Intern Med 130(7): 545-53.
This survey of women showed that estrogen use was more common in the South and West, and that it was more common in women who had more education.
February 1999: Medroxyprogesterone-acetate (Depo-provera) contraception is associated with decreased bone density. Scholes, D.(1999). Bone mineral density in women using depot medroxyprogesterone acetate for contraception. Obstet Gynecol 93(2): 233-8.
In this population-based study of 457 women the bone density was lower in the 183 recruited because they were using depo-medroxyprogesterone for contraception. In the youngest age group (18-21) the bone density was 10.5% lower in the ones who used this form of contraception, and those who had been using it the longest had the greatest loss.
Click to go to the page of what was new in 1998.