help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2004-1350
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Frassetto, L.
Right arrow Articles by Sebastian, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Frassetto, L.
Right arrow Articles by Sebastian, A.
Related Collections
Right arrow Calcium and Bone Metabolism
The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 2 831-834
Copyright © 2005 by The Endocrine Society

Long-Term Persistence of the Urine Calcium-Lowering Effect of Potassium Bicarbonate in Postmenopausal Women

Lynda Frassetto, R. Curtis Morris, Jr. and Anthony Sebastian

Department of Medicine (L.F., R.C.M., A.S.) and General Clinical Research Center (L.F., A.S.), University of California, San Francisco, San Francisco, California 94143

Address all correspondence and requests for reprints to: Lynda Frassetto, University of California, San Francisco, Box 0126, San Francisco, California 94143. E-mail: frassett{at}gcrc.ucsf.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Potassium bicarbonate (KBC) potently reduces urine calcium excretion in adult humans, including patients with hypertension or calcium urolithiasis, and postmenopausal women. In the latter, who have substantial risk of calcium deficiency, it remains unknown whether the observed short-term urine calcium-lowering effect of KBC persists over years.

We studied 170 postmenopausal women randomized to KBC 30, 60, or 90 mmol/d (KBC treatment), or placebo, for up to 36 months. Each received a multivitamin with 400 IU vitamin D, and calcium carbonate as needed to produce a total dietary calcium intake of at least 30 mmol daily.

Daily urine calcium excretion (UCaV) did not differ among groups at baseline (all-groups mean ± SD, 155 ± 83 mg/d). From 1–36 months of KBC treatment, adjusting UCaV for creatinine (Cr) excretion, each dose of KBC reduced UCaV (P < 0.01) with a dose-dependent trend (P = 0.05). The reduced UCaV/Cr persisted throughout the KBC treatment period (up to 36 months) in all KBC, and the greatest reductions occurred in the subjects with greatest baseline UCaV/Cr ({Delta}UCaV/Cr vs. baseline UCaV/Cr; P < 0.001).

Twenty-eight percent of the subjects had high baseline calciuria (UCaV/Cr > 200 mg Ca/1000 mg Cr). With baseline UCaV/Cr of 250 mg/1000 mg Cr, KBC 60 mmol decreased UCaV/Cr by 55.8 mg/1000 mg Cr, a potential daily calcium retention that over a 36-month period would accumulate up to 55,845 mg of calcium, nearly 5% of bone calcium content.

KBC treatment induced a dose-dependent decrease in UCaV/Cr that persisted up to 36 months, with the greatest decreases occurring in those women with the greatest baseline UCaV, nearly a third of whom had high baseline calciuria. Thus, one can preselect postmenopausal women most likely to have the urine calcium-lowering effect of KBC and predict their potential bone calcium increase.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
AGE-RELATED BONE MASS decline entails loss of bone calcium. Bone might lose calcium in part because its alkaline calcium salts titrate noncarbonic acids endogenously produced in response to habitual ingestion of the net acid-producing diets typical of Western countries (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11). The acid-liberated bone calcium disappears in urine, proportionate to the magnitude of the diet net acid load (12). Although the kidney daily excretes the bulk of the diet net acid load, the body retains a small fraction sufficient to induce a persisting low-grade metabolic acidosis, which ensures continued titration of the alkaline salts of bone, with attendant loss of calcium and phosphorus in urine (5, 14, 15, 16).1 The diet-induced low-grade metabolic acidosis that persists further contributes to the external losses of calcium by direct impairment of renal calcium reabsorptive efficiency, a characteristic of metabolic acidosis (17).

Eating a diet that produces little or no net acid, or neutralizing the diet’s acid with an exogenously administered basic salt such as potassium bicarbonate (KBC), decreases the demand for bone base, hence presumably decreases the amount of bone breakdown and amount of bone calcium released (6, 9, 18). This in turn leads to a decrease in urine calcium excretion (7, 9, 12, 19, 20).

Previously, we demonstrated, in 18 postmenopausal women fed a nutritionally standard, high-protein diet for 2 months supplemented with KBC (60–120 mmol/d for 18 d), that plasma bicarbonate increased significantly (P = 0.03) and that net acid production, as estimated by renal net acid excretion, decreased (P < 0.001) (9), greater in the women taking the 120-mmol dose of KHCO3 than in the women taking the 60-mmol dose. Calcium balance improved, slightly more so in the group given the higher dose of KHCO3, and in all subjects the improvement in calcium balance was mirrored by an improvement in phosphate balance. Other investigators have also shown a short-term effect of KBC or citrate to lower urine calcium excretion (7, 12, 19, 20).

The question remains whether the urine calcium-lowering effect of KBC persists over years, as would be necessary to substantially improve or prevent bone lost from its titration by endogenous produced noncarbonic acids. However, such a persisting effect remains undemonstrated. Accordingly, we undertook the present study to evaluate the long-term effects on urine calcium excretion of continued titration of the diet net acid load with different doses of KBC.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
We enrolled 201 women in this 3-yr trial; 170 women returned for at least two follow-up visits and were included in this analysis. All of the women completed menopause at least 5 yr previously and had not taken estrogen, bisphosphonates, or thiazide diuretics ever or for at least 2 yr before the study. They averaged 61 ± 7 yr of age, and body mass index (BMI) was 25 ± 4 kg/m2. They included 149 Caucasian, 17 Asian, and four Hispanic (Table 1Go). These figures reflect the demographics of the recruitment area (San Francisco and Marin County). The study was conducted after approval by the Institutional Review Board of the University of California, San Francisco, and informed consent was obtained from all of the women. None of the subjects or results in the present study have been reported previously. We excluded subjects with renal or cardiac disease, parathyroid or thyroid dysfunction, and osteoporosis at baseline (as determined by dual-energy x-ray absorptiometry). We collected 24-h urine specimens for determination of creatinine (Cr) clearance and urine mineral and electrolyte concentration before the subjects were randomized.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Baseline data for each group

 
After qualifying for the study, we randomized subjects to placebo or KHCO3, either 30, 60, or 90 mmol/d, given in three divided doses with meals. One third of all subjects were randomized to placebo, one third to 60 mmol of potassium, and the remaining one third to either 30 or 90 mmol of potassium. After evaluating dietary intake, we gave calcium supplements (calcium carbonate) if necessary to ensure a dietary intake of calcium of at least 1200 mg/d (30 mmol/d). All subjects also received a vitamin D supplement of 400 IU.

We followed subjects at 1 month and then every 3 months for up to 36 months with repeated blood samples and 24-h urine samples for calcium, sodium, potassium, chloride, phosphate, and Cr. For calculation of changes in calcium excretion, we used the values at month 1 as the first measuring point because at baseline subjects had not yet been put on calcium supplementation if needed to raise their dietary calcium intake to approximately 1200 mg/d (30 mmol/d). For most analyses, we used the Cr adjusted values of urine calcium excretion to minimize errors caused by variability in collection. Compliance was judged by urinary potassium excretion.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Table 1Go shows the baseline characteristics of the subjects. At baseline, urine calcium excretion averaged 156 ± 78 mg/d (3.9 ± 2.0 mmol/d) for all subjects, and the values among groups did not differ significantly. Twenty-eight percent of the subjects had baseline urine calcium excretion greater than 250 mg/1000 mg Cr (71 mmol/100 mmol Cr). Creatinine clearance for all subjects averaged 83 ± 19 ml/min at baseline.

Table 2Go shows that, compared with placebo, daily urine calcium excretion [UCaV/Cr, mg/1000 mg Cr (mmol/88 mol Cr converted to mmol/100 mmol Cr)] decreased significantly in each of the KBC groups. Values for urine calcium change represent the average change over the period of 12–36 months.


View this table:
[in this window]
[in a new window]
  		TABLE 2. UCaV difference from placebo

 
Figure 1Go shows that from 12–36 months of treatment, adjusting for Cr excretion, KBC 30, 60, and 90 mmol/d lowered urine calcium (UCaV/Cr) relative to placebo (P < 0.01), with a dose-dependent trend (P = 0.05), with placebo included, although with no significant difference between the 60- and 90-mmol/d KBC dose.



View larger version (21K):
[in this window]
[in a new window]
  		FIG. 1. Dose-dependent decrease in urine calcium excretion (mg Ca/1000 mg Cr) from month 1 with KBC administration (data shown are the averages of months 12–36 for each group; P = 0.05). (To convert to millimoles, divide milligrams of Ca by 40 and milligrams of Cr by 113.)

 
Table 3Go and Fig. 2Go show that the greatest reductions in UCaV/Cr occurred in the subjects with greatest baseline UCaV/Cr [{Delta}UCaV/Cr vs. baseline UCaV/Cr; P < 0.001 for each dose (Table 3Go) and P < 0.01 for all doses (Fig. 2Go)]. Figure 2Go also shows that relationship for the 60-mmol/d dose of KBC at 36 months.


View this table:
[in this window]
[in a new window]
  		TABLE 3. {Delta}UCaV vs. baseline UCaV (mg Ca/1000 mg Cr)

 


View larger version (28K):
[in this window]
[in a new window]
  		FIG. 2. Decline in urine calcium excretion (mg Ca/1000 mg Cr) from month 1 in individual subjects at month 24 (all groups receiving KBC) and month 36 (subjects in the largest group receiving 60 mmol KBC). (To convert to millimoles, divide milligrams of Ca by 40 and milligrams of Cr by 113.)

 
Both urine potassium excretion and pH increased in the KHCO3 treatment groups. Compared with baseline, urine potassium excretion increased 31.8 ± 33.0, 50.6 ± 28.6, and 72.9 ± 33.7 mEq (mmol) per day in the 30-, 60-, and 90-mmol KHCO3 groups, averaged over the 36-month period (P < 0.05 for all paired comparisons between treatment groups and against placebo). During KBC treatment, urine pH values averaged as follows: placebo, 6.49; KHCO3 30 mEq/d, 7.00; KHCO3 60 mEq/d, 7.01; and KHCO3 90 mEq/d, 7.20 (Fig. 3Go). Multiple comparisons testing by Dunn’s method revealed that placebo was significantly different from each KHCO3 dose, at a tested level of P < 0.05, and no significant differences between any two KHCO3 doses (mEq/d: 30 vs. 60, 60 vs. 90, and 30 vs. 90)



View larger version (18K):
[in this window]
[in a new window]
  		FIG. 3. Effect of KBC on urine pH, by dose and duration of administration.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
This study demonstrates that in normal postmenopausal women eating a typical American diet, supplementing dietary potassium with potassium bicarbonate induces a reduction in urinary excretion of calcium that persists over a period of up to 36 months. More importantly, the women at the greatest risk for body calcium loss (i.e. hypercalciuric subjects at baseline) had the greatest decline in urinary excretion of calcium and would potentially derive the greatest benefit from treatment with potassium bicarbonate.

Assuming a urine calcium excretion at baseline of 250 mg/1000 mg Cr (71 mmol/100 mmol Cr), a woman receiving 60 mmol/d of KHCO3 would have a decrease in urinary excretion of calcium of approximately 55 mg/1000 mg Cr per day (15.5 mmol/100 mmol Cr per day). Because absolute Cr excretion averaged 931 mg/d in this group, a reduction of 55 mg Ca/1000 mg Cr per day converts to an absolute reduction of 51 mg Ca per day. Retained over 36 months, without change in intestinal calcium absorption, this amount of calcium would accumulate to more than 55,845 mg (1396 mmol) of calcium, a potential saving of bone calcium content of nearly 5%, assuming a total bone calcium content of approximately 1200 g (21). Previous studies with KHCO3 administration confirm no change in intestinal calcium absorption (9, 22). Yet, no one has studied the effect of long-term (months or years) of KHCO3 administration on intestinal calcium absorption. Because body calcium content increases because of renal calcium retention, intestinal calcium absorption might decrease, perhaps secondary to reduced PTH-driven calcitriol production. Yet, even if intestinal calcium absorption decreases over time (months or years), unless it does so commensurately with the reduction in urine calcium excretion, calcium balance will remain on the positive side.

Many factors can affect urine calcium excretion, including dietary calcium and sodium intake, vitamin D intake, PTH levels, thyroid function, and renal function. At baseline, these factors did not differ among subgroups (Table 1Go). Sodium intake, as judged by urine sodium excretion, remained unchanged within and between groups during the 36 months of the study. A nonsignificant decline in renal function occurred in all groups over time, with the slope of the change in renal function nearly identical in all groups.

More than one quarter of the women in this study had high baseline calciuria. High urine calcium excretion is often seen in women with osteoporosis and can be an important predictor for both low bone mass (23, 24, 25) and kidney stones (26). Supplementation of the diet with a potassium alkalinizing salt has been shown to decrease the incidence of kidney stones in subjects with a propensity to form kidney stones (27) and to prevent bone loss in patients with calcium urolithiasis (28) and reduce bone resorption in postmenopausal women (6). This study suggests that one can preselect the postmenopausal women most likely to benefit from long term KHCO3 and potentially decrease the incidence of osteoporosis.


   Acknowledgments
 
We thank Steven Harris, M.D., Eileen Nash, R.N., and the General Clinical Research Center staff for their generous help with this study.


   Footnotes
 
This study was supported by the General Clinical Research Center with funds provided by the National Center for Research Resources (M01 RR-00079) and gifts from Church & Dwight Co., Inc., and the Emil Mosbacher, Jr., Foundation.

First Published Online November 30, 2004

Abbreviations: Cr, Creatinine; KBC, potassium bicarbonate; UCaV, urine calcium excretion.

1 Although plasma acidity does not perceptibly increase from day to day (5 ), a gradual increase does occur over time as renal acid-base regulatory function declines with increasing age (13 ). Therefore, although it appears that bone completely neutralizes the small fraction of retained acid daily, an even smaller fraction escapes bone neutralization and a slight retention of acid accumulates in body fluids to account for the increasing acidity with advancing age. Back

Received July 12, 2004.

Accepted November 18, 2004.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Bushinsky DA, Frick KK 2000 The effects of acid on bone. Curr Opin Nephrol Hypertens 9:369–379[CrossRef][Medline]
  2. Morris Jr RC, Frassetto LA, Schmidlin O, Forman A, Sebastian A 2001 Expression of osteoporosis as determined by diet-disordered electrolyte and acid-base metabolism. In: Burckhardt P, Dawson-Hughes B, Heaney RP, eds. Nutritional aspects of osteoporosis. San Diego: Academic Press; 357–378
  3. Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris Jr RC 2002 Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors. Am J Clin Nutr 76:1308–1316[Abstract/Free Full Text]
  4. Frassetto LA, Todd KM, Morris Jr RC, Sebastian A 2000 Worldwide incidence of hip fracture in elderly women: relation to consumption of animal and vegetable foods. J Gerontol A Biol Sci Med Sci 55:M585–M592
  5. Kurtz I, Maher T, Hulter HN, Schambelan M, Sebastian A 1983 Effect of diet on plasma acid-base composition in normal humans. Kidney Int 24:670–680[Medline]
  6. Marangella M, Di Stefano M, Casalis S, Berutti S, D’Amelio P, Isaia GC 2004 Effects of potassium citrate supplementation on bone metabolism. Calcif Tissue Int 74:330–335[CrossRef][Medline]
  7. Maurer M, Riesen W, Muser J, Hulter HN, Krapf R 2003 Neutralization of Western diet inhibits bone resorption independently of K intake and reduces cortisol secretion in humans. Am J Physiol Renal Physiol 284:F32–F40
  8. New SA, Macdonald HM, Campbell MK, Martin JC, Garton MJ, Robins SP, Reid DM 2004 Lower estimates of net endogenous non-carbonic acid production are positively associated with indexes of bone health in premenopausal and perimenopausal women. Am J Clin Nutr 79:131–138[Abstract/Free Full Text]
  9. Sebastian A, Harris ST, Ottaway JH, Todd KM, Morris Jr RC 1994 Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med 330:1776–1781[Abstract/Free Full Text]
  10. Sellmeyer DE, Stone KL, Sebastian A, Cummings SR 2001 A high ratio of dietary animal to vegetable protein increases the rate of bone loss and the risk of fracture in postmenopausal women. Study of Osteoporotic Fractures Research Group. Am J Clin Nutr 73:118–122[Abstract/Free Full Text]
  11. Wachman A, Bernstein DS 1968 Diet and osteoporosis. Lancet 1:958–959[Medline]
  12. Lemann Jr J 1999 Relationship between urinary calcium and net acid excretion as determined by dietary protein and potassium: a review. Nephron 81(Suppl 1):18–25
  13. Frassetto L, Morris Jr RC, Sebastian A 1996 Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline. Am J Physiol 271:1114–1122
  14. Alpern RJ 1995 Trade-offs in the adaptation to acidosis. Kidney Int 47:1205–1215[Medline]
  15. Alpern RJ, Sakhaee S 1997 The clinical spectrum of chronic metabolic acidosis: homeostatic mechanisms produce significant morbidity. Am J Kidney Dis 29:291–302[Medline]
  16. Frassetto L, Morris Jr RC, Sellmeyer DE, Todd K, Sebastian A 2001 Diet, evolution and aging–the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Eur J Nutr 40:200–213[CrossRef][Medline]
  17. Lemann Jr J, Litzow JR, Lennon EJ 1967 Studies of the mechanism by which chronic metabolic acidosis augments urinary calcium excretion in man. J Clin Invest 46:1318–1328[Medline]
  18. Lemann Jr J, Bushinsky DA, Hamm LL 2003 Bone buffering of acid and base in humans. Am J Physiol Renal Physiol 285:F811–F832
  19. Lemann Jr J, Gray RW, Pleuss JA 1991 Anti-calciuric diuretics and potassium bicarbonate reduce bone resorption in patients with idiopathic hypercalciuria. Clin Res 39:469A
  20. Lutz J 1984 Calcium balance and acid-base status of women as affected by increased protein intake and by sodium bicarbonate ingestion. Am J Clin Nutr 39:281–288[Abstract/Free Full Text]
  21. McCarthy JT, Kumar R 2004 Divalent cation metabolism: calcium. In: Schrier RW, ed. Atlas of diseases of the kidney, Vol 1. Disorders of water, electrolytes, and acid-base. Informatics Commission and NKF cyberNephrology; 6.1–6.14; http://www.kidneyatlas.org/book1/adk1_05.pdf
  22. Lemann Jr J, Gray RW, Pleuss JA 1989 Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men. Kidney Int 35:688–695[Medline]
  23. Giannini S, Nobile M, Dalle CL, Lodetti MG, Sella S, Vittadello G, Minicuci N, Crepaldi G 2003 Hypercalciuria is a common and important finding in postmenopausal women with osteoporosis. Eur J Endocrinol 149:209–213[Abstract]
  24. Nordin BE 1997 Calcium and osteoporosis. Nutrition 13:664–686[CrossRef][Medline]
  25. Nordin BE, Need AG, Morris HA, Horowitz M 1999 Biochemical variables in pre- and postmenopausal women: reconciling the calcium and estrogen hypotheses. Osteoporos Int 9:351–357[CrossRef][Medline]
  26. Cirillo M, Stellato D, Panarelli P, Laurenzi M, De Santo NG 2003 Cross-sectional and prospective data on urinary calcium and urinary stone disease. Kidney Int 63:2200–2206[CrossRef][Medline]
  27. Pak CYC 1994 Citrate and renal calculi: an update. Miner Electrolyte Metab 20:371–377[Medline]
  28. Pak CY, Peterson RD, Poindexter J 2002 Prevention of spinal bone loss by potassium citrate in cases of calcium urolithiasis. J Urol 168:31–34[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Am. J. Clin. Nutr.Home page
T. R Fenton, M. Eliasziw, A. W Lyon, S. C Tough, and D. A Hanley
Meta-analysis of the quantity of calcium excretion associated with the net acid excretion of the modern diet under the acid-ash diet hypothesis
Am. J. Clinical Nutrition, October 1, 2008; 88(4): 1159 - 1166.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Coll. Nutr.Home page
R. C. Morris Jr., O. Schmidlin, L. A. Frassetto, and A. Sebastian
Relationship and Interaction between Sodium and Potassium.
J. Am. Coll. Nutr., June 1, 2006; 25(3 Suppl): 262S - 270S.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
S. Berkemeyer and T. Remer
Anthropometrics Provide a Better Estimate of Urinary Organic Acid Anion Excretion than a Dietary Mineral Intake-Based Estimate in Children, Adolescents, and Young Adults
J. Nutr., May 1, 2006; 136(5): 1203 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Coll. Nutr.Home page
J.-P. Bonjour
Dietary Protein: An Essential Nutrient For Bone Health
J. Am. Coll. Nutr., December 1, 2005; 24(suppl_6): 526S - 536S.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Remer and S. Berkemeyer
Letter re: Persistent Hypocalciuric Effect of Potassium Bicarbonate in Postmenopausal Women
J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4980 - 4981.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. P. Heaney, K. Rafferty, and K. M. Davies
Letter re: Long-Term Persistence of the Urine Calcium-Lowering Effect of Potassium Bicarbonate in Postmenopausal Women
J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4417 - 4417.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Sebastian, L. Frassetto, and R. C. Morris Jr.
Authors' Response: Long-Term Persistence of the Urine Calcium-Lowering Effect of Potassium Bicarbonate in Postmenopausal Women
J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4417 - 4418.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Frassetto, L.
Right arrow Articles by Sebastian, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Frassetto, L.
Right arrow Articles by Sebastian, A.
Related Collections
Right arrow Calcium and Bone Metabolism

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals