Omaha Nuns Study

THE OMAHA NUNS STUDY

Purpose: The Omaha Nuns Study is an ongoing project, the purpose of which is to characterize the calcium economy in mid-life and aging women, to monitor changes in that economy with age, and to assess prospectively the nutritional, hormonal, disease, and lifestyle factors that affect bone status. “Economy” means the sum total of all of the flows of calcium into and out of the body, as well as the internal movement of calcium into and out of bone and the movement of calcium into the intestine in the form of digestive juices and the opposite movement from the intestine into the blood, as calcium absorption. As calcium is the principal cation of bone, changes in calcium balance translate immediately into changes in bone mass. Negative calcium balance means a woman is losing bone, and positive calcium balance means she is gaining.

History: The Omaha Nuns Study started in 1967 with a cohort of women average age 40. There were 191 enrolled overall and for the most part each has been followed on a 5-year cycle with intensive in-patient measurements of calcium movement into and out of the body and between the blood and the bone. These measurements were made during 8-day in-patient metabolic study periods, while consuming a constant fixed diet, with complete collection of excreta, and with measurement of blood calcium isotope concentration after oral and intravenous dosing with isotopic tracers.

Approach: The primary focus of the study has always been osteoporosis, the disease that is common in women after age 50 and is responsible for most of the fractures of late life, particularly at the spine, hip, and wrist. Our goal in this study was to detect the changes in the calcium economy that led up to the disorder, instead of waiting to measure what was going on after a woman had already developed the problem. Hence it seemed important to start with healthy women still 10–25 years away from manifesting osteoporosis. Nuns were the ideal study subjects because we knew that they got osteoporosis like everyone else and because they were more likely to be able to make the long-term commitment that a study of this sort required.

Results: As the study is continuing up to the present time, we still do not have final answers with respect to all the changes that may predict or predispose to osteoporosis, but in the process of following the women all these years we have provided to the scientific community the most complete mapping of the calcium economy of mid-life women that is available anywhere. The current calcium intake recommendations from the National Institutes of Health, from the National Osteoporosis Foundation, and from the Institute of Medicine, while using evidence from many other sources as well, have been based primarily on the results of studies performed here at Creighton on our cohort of nuns.

Those recommendations, in brief, as summarized in several NIH Consensus Conference documents, are that an intake of 1000 mg/day is required to maintain balance in a typical woman up to the time when she undergoes menopause and/or stops estrogen replacement therapy, and then, in the absence of estrogen, her calcium requirement typically rises to about 1500 mg/day. The bone loss that occurs in women following menopause is partly due to this increase in the requirement (which the average woman does not match with a corresponding increase in intake).

Our studies have also looked at the factors which influence how the body handles calcium, particularly the effect of other nutritional factors, with major emphasis on vitamin D, protein, phosphorus, and potassium. For example, results from the Omaha Nuns Study have shown clearly that women do a better job at using and retaining calcium if their protein intake is high and, of course, if their vitamin D status is normal as well.

The Omaha Nuns Study project explicitly recognizes that osteoporosis is a multifactorial disorder, with many factors contributing to the development of fragility fractures later in life. The study’s emphasis on nutritional factors is partly due to the fact that these are under our control, either as a society, or as individuals. While ensuring adequate nutrition will not prevent all osteoporotic fractures, it will prevent many of them. Current best estimates are that a high intake of calcium and vitamin D will reduce the risk of fractures that occur after menopause by from 40 to 55%.

A listing of the publications resulting from this project to date follows.

PEER-REVIEWED SCIENTIFIC PAPERS BASED ON OMAHA NUNS STUDY

Heaney RP, Saville PD, Recker RR. Calcium absorption as a function of calcium intake. J Lab Clin Med 85:881-890, 1975.

Saville PD, Heaney RP, Recker RR. Radiogrammetry at four bone sites in normal middle-aged women: Their relation to each other, to calcium metabolism and to other biological variables. Clin Orthop 114:307-315, 1976.

Heaney RP, Recker RR, Saville PD. Menopausal changes in bone remodeling. J Lab Clin Med 92:964-970, 1978.

Heaney RP, Recker RR, Saville PD. Menopausal changes in calcium balance performance. J Lab Clin Med 92:953-963, 1978.

Heaney RP, Recker RR. Effects of nitrogen, phosphorus, and caffeine on calcium balance in women. J Lab Clin Med 99:46-55, 1982.

Heaney RP, Recker RR. Estimation of true calcium absorption. Ann Int Med 103:516-521, 1985.

Heaney RP, Recker RR. Distribution of calcium absorption in middle-aged women. Am J Clin Nutr 43:299-305, 1986.

Heaney RP, Recker RR, Hinders SM. Variability of calcium absorption. Am J Clin Nutr 47:262-264, 1988.

Barger-Lux MJ, Heaney RP, Recker RR. Time course of calcium absorption in humans: evidence for a colonic component. Calcif Tissue Int 44:308-311, 1989.

Davies KM, Recker RR, Heaney RP. Normal vertebral dimensions and normal variation in serial measurements of vertebrae. J Bone Miner Res 4:341-349, 1989.

Heaney RP, Recker RR, Stegman MR, Moy AJ. Calcium absorption in women: relationships to calcium intake, estrogen status, and age. J Bone Miner Res 4:469-475, 1989.

Heaney RP, Davies KM, Recker RR, Packard PT. Long-term consistency of nutrient intakes. J Nutr 120:869-875, 1990.

Heaney RP. Fecal calcium density: a measure of calcium compliance. J Bone Miner Res 6:469-471, 1991.

Davies KM, Recker RR, Stegman MR, Heaney RP. Tallness vs. shrinkage: are women shrinking with age or growing taller with recent birthdate? J Bone Miner Res 6:1115-1120, 1991.

Davies KM, Recker RR, and Heaney RP. Revisable criteria for vertebral deformity. Osteoporosis Int 3:265-270, 1993.

Heaney RP, Recker RR. Determinants of endogenous fecal calcium in healthy women. J Bone Miner Res 9:1621-1627, 1994.

Abrams SA, Yergey AL, Heaney RP. Relationship between balance and dual tracer isotopic measurements of calcium absorption and excretion. J Clin Endocrinol Metab 79:965-969, 1994.

Barger-Lux MJ, Heaney RP. Caffeine and the calcium economy revisited. Osteoporos Int 5:97-102, 1995.

Heaney RP, Barger-Lux MJ, Davies KM, Ryan RA, Johnson ML, Gong G. Bone dimensional change with age: interactions of genetic, hormonal, and body size variables. Osteoporos Int 7:426-431, 1997.

Heaney RP, Recker RR, Ryan RA. Urinary calcium in perimenopausal women: normative values. Osteoporos Int 9:13-18, 1999.

Gong G, Johnson ML, Barger-Lux MJ, Heaney RP. Association of bone dimensions with a parathyroid hormone gene polymorphism in women. Osteoporos Int 9:307-311, 1999.

Freeman SPHT, Beck B, Bierman JM, Caffee MW, Heaney RP, Holloway L, Marcus R, Southon JR, Vogel JS. The study of skeletal calcium metabolism with 41Ca and 45Ca. Nuclear Instruments and Methods in Physics Research B (NIMB) August 2000.

Davies KM, Heaney RP, Recker RR, Lappe JM, Barger-Lux MJ, Rafferty K, Hinders S. Calcium intake and body weight. J Clin Endocrinol Metab 85:4635-4638, 2000.

Davies KM, Heaney RP, Recker RR, Barger-Lux MJ, Lappe JM. Hormones, weight change, and menopause. Int J Obesity 25:874-879, 2001.

Davies KM, Heaney RP, Rafferty K. Decline in muscle mass with age in women: a longitudinal study using an indirect measure. Metabolism 51(7):935-939, 2002.

Heaney RP, Nordin BEC. Calcium effects on phosphorus absorption: implications for the prevention and co-therapy of osteoporosis. J Am Coll Nutr 21(3):239-244, 2002.

Heaney RP, Davies KM, Barger-Lux MJ. Calcium and weight: clinical studies. J Am Coll Nutr 21(2):152S-155S, 2002.

Heaney RP, Abrams SA. Improved estimation of the calcium content of total digestive secretions. J Clin Endocrinol Metab 89:1193-1195, 2004.

Davies KM, Rafferty K, Heaney RP. Determinants of endogenous calcium entry into the gut. Am J Clin Nutr Am J Clin Nutr 80(4):919-923, 2004.

Rafferty K, Davies KM, Heaney RP. Potassium intake and the calcium economy. J Am Coll Nutr 24(2):99-106, 2005.

Barger-Lux MJ, Heaney RP. Calcium absorptive efficiency is positively related to body size. J Clin Endocrinol Metab 90:5118-5120, 2005.

Heaney RP. Effects of protein on the calcium economy. In: Nutritional Aspects of Osteoporosis. Burckhardt P, Dawson-Hughes B, Heaney RP, eds. Elsevier Inc., Amsterdam, (in press) April 2007.