What was NEW in 1998?

Abstracts from the American Society for Bone and Mineral Research and International Bone and Mineral Society combined meeting, December 1-6, 1998.

These are the ones that I thought were most relevant to osteoporosis. Here are the brief summaries

Bone Mass and High Dietary Intake of Meat and Protein: Analyses of Data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-94). Mona S. Calvo, Curtis N. Barton*, Youngmee K. Park*. Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, DC. . . .our findings suggest that high intake of meat, poultry, fish, and eggs or a high protein intake are not associated with lower bone mass and greater risk of osteoporosis. However, we caution against over-interpretation of our results given the limitations of the cross- sectional survey design.

Animal and Nonanimal Dietary Protein: What Are Effects on Bone Loss in Elders of the Framingham Osteoporosis Study? M. T. Hannan, K. Tucker*, B. Dawson-Hughes, D. Felson, D. P. Kiel. Harvard Med Sch, Hebrew Rehab Ctr for Aged, HNRC at Tufts Univ, Boston Univ, Boston, MA. Contrary to expectations, elders with higher animal protein intake had reduced bone loss, suggesting that typical population intakes of animal protein within the range commonly consumed do not result in bone loss.

Calcium Supplementation Enhances Increases in Bone Mineral Density of Young Adult Women. N. Kathryn Henderson, Roger I. Price, Donald H. Gutteridge, Joan H. Cole, Robert W. Retallack, Wendy Green. Endocrinology and Diabetes, Medical Technology and Physics, Sir Charles Gairdner Hospital, Perth, WA, Australia, School of Physiotherapy, Curtin University of Technology, Perth, WA, Australia, Bone and Mineral Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.

The Effect of 2 and 3 Years of Raloxifene on Vertebral and Non-Vertebral Fractures in Postmenopausal Women with Osteoporosis. K. Ensrud, D. Black, R. Recker, S. Harris, P. Delmas, H. Pols, J. Reginster, N. Bjarnason, C. Gennari, H. Genant, R. Knickerbocker, R. Eastell, J. Adachi, B. Mitlak, for the MORE Study Group. U of MN, U of CA, San Francisco, Creighton U, Hopital E., Herriot, France, Andromed, The Netherlands, Policliniques Universitaires L. Brull, Belgium, CCBR, Denmark, Istituto di Patologia Speciale Medica, Italy, Eli Lilly, Indianapolis, IN, University of Sheffield, England, McMaster U, Canada. MORE enrolled 7705 women . . . randomized to placebo, raloxifene 60 mg/day or raloxifene 120 mg/day; In both substudies, significant reductions in risk of incident vertebral Fxs were observed for both 60 mg and 120 mg doses of raloxifene. Go to SERMs

Postmenopausal Women with Osteoporosis: Effects of Raloxifene on Bone Mineral Density in the Hip and Lumbar Spine. P. J. Meunier, E. Vignot*, P. Garnero*, E. Confavreux*, E. Paris*, S. Sarkar*, S. Liu-Leage*, R. Knickerbocker, T. Nickelsen, M. Wong*, M. W. Draper. Service de Rhumatologie et de Pathologie Osseuse, Hopital Edouard Herriot, Lyon, France, Centre Lyonnais d'Investigation des Osteoporoses, Lyon, France, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, USA, Lilly France, Saint Cloud, France, 5 Lilly Deutschland GmbH, Bad Homburg, Germany. In summary, 12-month raloxifene therapy in postmenopausal osteoporotic women significantly increased BMD in the total hip, hip subregions and lumbar spine.

Upper Gastrointestinal Symptoms and Noncompliance with Dosing Instructions Associated with Alendronate for Osteoporosis in a Large HMO. B. Ettinger, J. Schein*, A. Pressman*. Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA, Novartis Pharmaceuticals Corporation, East Hanover, NJ. . . . Nearly a third of the women reported new upper GI symptoms ascribed to alendronate use. A significant (p<0.05) difference in the rate of new ARD encounters was observed for women >=75 years, among whom alendronate users had a 2.1-fold higher ARD rate compared with nonusers.

How many women lose bone while taking HRT? The PEPI Study. Gail A. Greendale, Robert Marcus, Bradley Wells*. UCLA, Stanford University, and Wake Forest Schools of Medicine, Los Angeles, CA. . . . At the spine, the %-loss cutpoints that defined "true" bone loss were - 3.08% (95% certain of bone loss), -2.59% (90% certain of bone loss), and -1.57% loss (68.3% certain of bone loss). At the hip, the corresponding figures were - 2.67%, - 2.24%, and - 1.36%. . . . Conclusion: Few women who adhere to HRT actually lose bone. Apparent losses during the initial year of treatment more likely represent measurement imprecision than true bone loss.

Bone Saving Effects of Low Dose Continuous Estrogen/Progestin with Calcium and Vitamin D in Elderly Women: A Randomized, Controlled Trial. R. R. Recker, K. M. Davies, R. M. Dowd, R. P. Heaney. Osteoporosis Research Center, Creighton University, Omaha, Nebraska. . . . We conclude that continuous low-dose HRT with CEE, 0.3 mg/d, and MP, 2.5 mg/d orally combined with adequate calcium and vitamin D provides a bone sparing effect comparable or superior to other, higher dose HRT regimens in elderly women, and is easily tolerated by most. [note: this now published, see June 99 entry]

Physical Mapping and Characterization of the High Bone Mass (HBM) Gene Region. M. L. Johnson, M. Lappe*, G. Gong, R. R. Recker, R. Little*, R. Del Mastro*, M. Osborne, C. Tulig*, J. Carulli. Human Genetics, Genome Therapeutics Corporation, Waltham, MA, Osteoporosis Research Center, Creighton University, Omaha, NE. Identification of the HBM gene will allow screening to determine whether this locus contributes to variation in BMD in the general population, and will also provide new targets for development of bone formation promoting drugs.

Effects of Alendronate and Estrogen, Alone or in Combination, on Bone Mass and Turnover in Postmenopausal Osteoporosis. S. Greenspan, A. Bankhurst*, N. Bell, M. Bolognese, H. Bone, M. Davidson*, R. Downs, R. Emkey, C. McKeever*, S. Miller*, A. Mulloy, S. Weiss, N. Heyden*, A. Lombardi, S. Suryawanshi*. Beth Israel Deaconess Med Ctr, Boston, MA, Univ of NM Sch of Med, Albuquerque, NM, Med Univ of SC, Charleston, SC, Osteoporosis Clinic, Gaithersburg, MD, Michigan Bone & Mineral Clinic, Detroit, MI, Chicago Ctr for Clin Res, Chicago, IL, Med College of VA, Richmond, VA, Reading Hospital, Reading, PA, ReSearch for Health, Houston, TX, SAM Clin Res, San Antonio, TX, Med College of GA, Augusta, GA, San Diego Endocrine & Med Clinic, San Diego, CA, Merck & Co, Rahway, NJ. . . . 425 hysterectomized, postmenopausal women age >=45yr with a spine BMD T-score <=-2. . .In summary, both ALN and CE increased spine and hip BMD in hysterectomized, postmenopausal osteoporotic women. COMB increased spine and femoral neck BMD more than either ALN or CE alone;

Salmon Calcitonin Nasal Spray (NS-CT) Reduces Risk of Vertebral Fracture(s) (VF) in Established Osteoporosis and Has Continuous Efficacy with Prolonged Treatment: Accrued 5 Year Worldwide Data of The PROOF Study. Stuart L. Silverman, Charles Chesnut, Kim Andriano, Harry Genant, Alberto Gimona, Michael Maricic, John Stock, David Baylink for the PROOF Study Group--. UCLA, Los Angeles, CA, Univ of Washington, Seattle, WA, Novartis Pharma, Basil CH and East Hanover, NJ, Univ California San Francisco, San Francisco, CA, Univ Arizona, Tucson, AZ, Mem. Health Care, Worcester, MA, Loma Linda Univ., Loma Linda, CA. . . . 5 year double blind, randomized placebo controlled study of 1,255 postmenopausal women worldwide . . . We found that the rate of new and/or worsening VF was . . . 39% lower (p=.03) in the 200 IU than in the PL group. . . The 100 IU and 400 IU groups showed improvements in the above fracture indices, but they did not reach statistical significance.

A Randomized Controlled Multi-Center Study of 1-84hPTH for Treatment of Postmenopausal Osteoporosis. Robert Lindsay, Anthony Hodsman, Harry Genant, Michael Bolognese, Mark Ettinger, for the PTH working group. Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, St. Joseph's Health Center, Lonton, Ontario, Canada, UCSF, San Francisco, CA, Gaithersburg, MD, Stuart, FL. . . . Women aged 50-75 yrs (mean 64.5 yrs) with osteoporosis (n=217) . . . BMD of lumbar spine increased in a dose dependent fashion, with increases of 2.6, 4.6, and 6.9% respectively (p<0.001) after one year with no significant change in the placebo group. Hip BMD did not change significantly.

Long-term Treatment with Alendronate Prevents Postmenopausal Bone Loss: Epic Four-Year Results. P. Ravn, N. H. Bjarnason, R. Wasnich, J. Davis, M. McClung, A. Balske*, D. Hosking, C. Chilvers*, A. Kaur*, M. Daley*, G. Cizza, for the EPIC Study Group. CCBR, Ballerup, Denmark, Merck Research Labs, Rahway, NJ, USA, City Hospital, Nottingham, UK, Osteoporosis Research Center, Portland, OR, Hawaii Osteoporosis Center, HI. . . . 1609 healthy post-menopausal women aged 45-59 years. . . . increases observed with the European formulation of E/P were substantially greater than those observed with either the US formulation or ALN 5 mg.

Effects of Alendronate for Two Years on BMD and Fractures in Patients Receiving Glucocorticoids. K. Saag, R. Emkey, A. Cividino, J. Brown, S. Goemaere, T. Dumortier*, A. G. Daifotis, M. Czachur*, for the Alendronate Study. The University of Iowa Hospitals and Clinics, Iowa City, IA, Bone Research Center, West Reading, PA, St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada, Le Centre hospitalier universitaire de Quebec, Quebec, Canada, U.Z. Gent, Gent, Belgium, Merck Research Laboratories, Rahway, NJ. . . . 208 patients remained on prednisone >=7.5 mg/day. . . BMD increased on ALN after 2 years in the lumbar spine and trochanter (p<0.01) and was maintained in the femoral neck. Relative to placebo, ALN 5 and 10 mg significantly increased BMD at all sites.

September 25, 1998 - How SERMs work

Jordan, V. Craig: Designer Estrogens. Scientific American, October 1998, Vol 279 P. 60

For all of you who have been meaning to learn more about these fascinating medications (tamoxifen, raloxifene) that hold promise for decreasing breast cancer, skeletal fractures, and heart attacks. Nice illustrations (except the artist's conception of an osteoporotic bone, which does not show osteoporosis but a bone surface almost entirely covered with resorption.)

September, 1998 - More disagreement about fluoride

Meunier, P J, Sebert, J L, Reginster, J Y, et al: Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis. Osteoporos-Int, 1998, 8:4.

Reginster, J Y, et al. The effect of sodium monofluorophosphate plus calcium on vertebral fracture rate in postmenopausal women with moderate osteoporosis. Annals Internal Medicine, 1998; 129:1.

The first study found no benefit, the second found a decreased rate of vertebral fractures with fluoride. In the second study peripheral fractures occured at the same rate. Hip fractures, the biggest concern about long-term fluoride therapy, occurred in only one patient in each group. There were some inconsistencies in that paper - the patients were said to have bone density T scores lower than -2.5. At the hip the mean score was .756 mg/cm2 - which is much higher than the the values reported in the NHANES study, in which osteoporosis was lower than .664 mg/cm2. They stated that two patients receiving hormones had a fracture, but when they excluded them from analysis the number of patients with fractures was the same as before. Interestingly, in the calcium group 5/8 of the fractures were seen in the first year of the 4 year study.

In my opinion, what we need is a study of fluoride plus estrogen vs estrogen alone in women who have low bone formation rates.

July, 1998 - Review of phytoestrogens

DM Tham, CD Gardner & WL Haskell, Journal of Clinical Endocrinology & Metabolism 1998,83:2223.

This is a good review of these interesting compounds. Many of my patients want to know if they can substitute for estrogen to prevent osteoporosis. After reading the review I discovered that my lack of knowledge about phytoestrogens and bone effects was not due to my negligence but to the dearth of data on the subject. So we will have to wait for more studies . . .

May 15, 1998 - Most vertebral fractures are painless, but they markedly increase risk of another fracture

Nevitt, Michael et al. The Association of radiographically detected vertebral fractures with back pain and function: A prospective study. Annals Internal Medicine 1998, 128:793.

This study xrayed spines of 7223 women older than 65 and repeated them 3.7 years later. During that time 371 women had a new vertebral fracture. This study again documented that prevalent fractures were an important risk factor for new fractures: In those without a fracture, 3.0% developed one, and in those with a fracture at baseline 13.8% had a new one.

Women were asked carefully about pain and disability symptoms. Increased back pain was experienced in 22% of women who did not have a new fracture and 38% of women who did have a new fracture.

These findings are similar to those in clinical trials, in which new vertebral fractures are found by xrays but only a minority of patients were aware of the occurance of the fracture. I think this has several implications for the management of osteoporosis. Since vertebral fractures strongly predict future fractures, and since many of them are "silent", it makes sense to recommend spine xrays as part of the evaluation of patients at risk for osteoporosis.

May 22, 1998 -Some news about weight

Langlois, J et al. Hip fracture risk in older white men is associated with change in body weight from age 50 years to old age". Arch Intern Med 1998;158:990.

This study shows that weight affects hip fracture in men, too. The results are similar to those in women. Men who lost 10% of weight since age 50 were 1.8 times as likely to have a hip fracture as those whose weight was not changed. On the other hand, men who had gained 10% of weight had a relative risk of 0.4 (I prefer to think in positive terms; this is a relative benefit of 2.5 times as likely to have an unfractured hip)

Espeland M. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. J Clin Endocrinol Metab 1997, 82:1549

This paper is not as new but seems to be unheralded. It reports data from the PEPI trial (Postmenopausal Estrogen/Progestin Intervention). Women who were randomly assigned to estrogen averaged 1.0 kg less weight gain after 3 years than those assigned to placebo. Furthermore, there was 1.2cm less increase in waist girth. Women taking estrogen and medroxyprogesterone gained 0.9 kg over 3 years while those on placebo gained 2.1 kg. Waist girth increased 1.5 cm in the hormone group but 2.8 cm in the placebo group. This data refutes the common myth that estrogen causes weight gain.

March 12, 1998 - Review of osteoporosis treatment

Eastell, R. Treatment of Postmenopausal Osteoporosis. New England Journal of Medicine 1998; 338:736

This is a nice summary of osteoporosis treatment. Some points I liked:

"[the T score] has limitations in clinical practice. It raises a risk factor for fracture to the status of a diagnostic criterion, ignores the importance of other determinanats of bone strength. . ."

"Estrogen replacement therapy is the treatment of first choice, because of long-term experience and its other benefits. . . "

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