Human lactation: Forearm trabecular bone loss, increased bone turnover, and renal conservation of calcium and inorganic phosphate with recovery of bone mass following weaning

The calcium (Ca) metabolism of established human lactation was studied in 40 adult women (mean age 32.4 years) who had been breast‐feeding for 6 months (Lac) and in 40 age‐matched controls (Con) using fasting urine and blood biochemistry and forearm single‐photon bone mineral densitometry (BMD). Serial studies were performed up to 6 months after weaning in Lac women and repeated once in Con women. During lactation the significant findings were (1) a selective reduction (7.1%, P < 0.03) in BMD at the ultradistal site containing 60% trabecular bone, but not at two more proximal, chiefly cortical bone sites; (2) increased bone turnover affecting bone resorption [fasting hydroxyproline excretion, Lac 2.22 + 0.12 μmol/liter GF (mean + SEM), Con 1.19 + 0.04, P < 0.001] and affecting bone formation (plasma alkaline phosphatase, Lac 81.9 + 2.5 IU/liter, Con 53.5 + 2.7, P < 0.001, and serum osteocalcin, Lac 14.0 + 0.7 μg/liter, Con 7.3 + 0.4, P < 0.001); and (3) renal conservation in the fasting state of both Ca and inorganic phosphate (Pi) with a resultant moderate increase in plasma Pi but not in plasma Ca (total or ionized). There were no differences between the groups in serum parathyroid hormone (PTH, intact and midmolecule assays), 25‐hydroxy‐ and 1,25‐dihydroxyvitamin D, nephrogenous cyclic AMP production, or plasma creatinine. In 25 of these Lac women restudied at one or more of the times 2, 4, or 6 months after weaning, the findings were (1) an early (2 months) normalization of bone resorption and renal Pi handling with continuing increased bone formation and renal Ca conservation, associated with the onset of increased intact PTH levels; and (2) a recovery, within 4‐6 months in ultradistal BMD associated with normalization of bone formation but with persisting renal Ca conservation and elevated intact PTH levels. We conclude that in established adult human lactation there is increased bone turnover with an accompanying loss of trabecular bone, despite renal conservation of Ca and Pi. After weaning, the deficit in trabecular bone is made up during a period of imbalance between a normal bone resorption rate and an elevated bone formation rate. The moderately elevated PTH after weaning may play a role in the recovery of bone mass by maintaining renal Ca conservation and by an anabolic action on bone.

[1]  G. Chan,et al.  Growth and bone mineralization of normal breast-fed infants and the effects of lactation on maternal bone mineral status. , 1982, The American journal of clinical nutrition.

[2]  J. Garel Hormonal control of calcium metabolism during the reproductive cycle in mammals. , 1987, Physiological reviews.

[3]  A. R. Frisancho,et al.  Unaltered cortical area of pregnant and lactating women. Studies of the second metacarpal bone in North and Central American populations. , 1971, Investigative radiology.

[4]  Millar Ra,et al.  LYONISATION OF THE X CHROMOSOME. , 1963 .

[5]  R. English,et al.  Nutrient intakes during pregnancy, lactation and after the cessation of lactation in a group of Australian women , 1968, British Journal of Nutrition.

[6]  C W Parker,et al.  Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. , 1972, The Journal of biological chemistry.

[7]  Williams Ln Semi-security and psychiatric hospitals. , 1974 .

[8]  G. Wardlaw,et al.  The effect of lactation on peak adult shaft and ultra-distal forearm bone mass in women. , 1986, The American journal of clinical nutrition.

[9]  B. Specker,et al.  Effect of Vegetarian Diet on Serum 1,25‐Dihydroxyvitamin D Concentrations During Lactation , 1987, Obstetrics and gynecology.

[10]  N. Butte,et al.  Effect of maternal diet and body composition on lactational performance. , 1984, The American journal of clinical nutrition.

[11]  G. Chan,et al.  Calcium intake and bone density of lactating women in their late childbearing years. , 1987, Journal of the American Dietetic Association.

[12]  J. Brundin,et al.  Changes of Bone Mineral Content During Pregnancy and Lactation , 1977, Acta obstetricia et gynecologica Scandinavica.

[13]  Rimoin Dl Familial metaphyseal dysplasia. , 1970, Lancet.

[14]  J L Kelsey,et al.  Epidemiology of osteoporosis and osteoporotic fractures. , 1985, Epidemiologic reviews.

[15]  G. Chan,et al.  Effects of increased dietary calcium intake upon the calcium and bone mineral status of lactating adolescent and adult women. , 1987, The American journal of clinical nutrition.

[16]  P. D. de Moor,et al.  Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. , 1981, The Journal of clinical investigation.

[17]  D. Baylink,et al.  Osteoporosis associated with pregnancy and lactation: bone biopsy and skeletal features in three patients. , 1984, Metabolic bone disease & related research.

[18]  J. Lian,et al.  Osteocalcin. Biochemical considerations and clinical applications. , 1988, Clinical orthopaedics and related research.

[19]  J. Kent,et al.  Parathyroid hormone radioimmunoassay: the clinical evaluation of assays using commercially available reagents. , 1985, Journal of immunoassay.

[20]  G. Rodan,et al.  Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. , 1988, Science.

[21]  J. Johnston,et al.  Bone mineral: effects of oral contraceptives, pregnancy, and lactation. , 1975, The Journal of bone and joint surgery. American volume.

[22]  J Reeve,et al.  Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial. , 1980, British medical journal.

[23]  B. Nordin DIAGNOSTIC PROCEDURES IN DISORDERS OF CALCIUM METABOLISM , 1978, Clinical endocrinology.

[24]  G. Chan,et al.  Bone mineral status of lactating mothers of different ages. , 1982, American journal of obstetrics and gynecology.

[25]  R. West,et al.  LOSS OF SKELETAL CALCIUM IN LACTATING WOMEN , 1970, The Journal of obstetrics and gynaecology of the British Commonwealth.

[26]  R. Prince,et al.  Forearm bone loss in hemiplegia: A model for the study of immobilization osteoporosis , 1988, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  K. Kivirikko,et al.  Modifications of a specific assay for hydroxyproline in urine. , 1967, Analytical biochemistry.

[28]  M. Whitehead,et al.  A PHYSIOLOGICAL ROLE FOR CALCITONIN: PROTECTION OF THE MATERNAL SKELETON , 1979, The Lancet.

[29]  D. Gutteridge,et al.  ESTIMATION OF 1,25 DIHYDROXYVITAMIN D BY CYTORECEPTOR AND COMPETITIVE PROTEIN BINDING ASSAYS WITHOUT HIGH PRESSURE LIQUID CHROMATOGRAPHY , 1985, Clinical endocrinology.

[30]  O. Bijvoet,et al.  NOMOGRAM FOR DERIVATION OF RENAL THRESHOLD PHOSPHATE CONCENTRATION , 1975, The Lancet.

[31]  R. Prince,et al.  Ultradistal and cortical forearm bone density in the assessment of postmenopausal bone loss and nonaxial fracture risk , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  J. Haddad,et al.  COMPETITIVE PROTEIN-BINDING RADIOASSAY FOR 25-HYDROXYCHOLECALCIFEROL1 , 1971 .

[33]  S. Atkinson,et al.  Changing osteocalcin concentrations during pregnancy and lactation: implications for maternal mineral metabolism. , 1987, The Journal of clinical endocrinology and metabolism.

[34]  B. Nordin,et al.  The tubular maximum for calcium reabsorption: normal range and correction for sodium excretion. , 1985, Clinica chimica acta; international journal of clinical chemistry.

[35]  E. Ritz,et al.  Effects of Hormones Other than Parathyroid Hormones on Renal Handling of Phosphate , 1980 .

[36]  J. Steichen,et al.  Mineral homeostasis during lactation- relationship to serum 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, parathyroid hormone and calcitonin. , 1982, The American journal of clinical nutrition.

[37]  M. Haussler,et al.  Control of mineral homeostasis during lactation: interrelationships of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone, calcitonin, prolactin, and estradiol. , 1981, American journal of obstetrics and gynecology.

[38]  J. Aloia,et al.  Determinants of bone mass in postmenopausal women. , 1983, Archives of internal medicine.

[39]  W. Duncan,et al.  The Effects of Lactation on Bone Mineral Content in Healthy Postpartum Women , 1989, Obstetrics and gynecology.

[40]  R. Brown,et al.  Circulating intact parathyroid hormone measured by a two-site immunochemiluminometric assay. , 1987, The Journal of clinical endocrinology and metabolism.

[41]  P. Price,et al.  Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. , 1980, Proceedings of the National Academy of Sciences of the United States of America.