Risk of calcium oxalate nephrolithiasis in postmenopausal women supplemented with calcium or combined calcium and estrogen

• Published in: Maturitas Vol. 41; no. 2; pp. 149 - 156
• Main Authors: Domrongkitchaiporn, Somnuek, Ongphiphadhanakul, Boonsong, Stitchantrakul, Wasana, Chansirikarn, Sirinthorn, Puavilai, Gobchai, Rajatanavin, Rajata
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 26-02-2002; Elsevier Science
• Subjects: Aged; Biological and medical sciences; Calcium Carbonate - administration & dosage; Calcium Carbonate - adverse effects; Calcium oxalate; Calcium Oxalate - urine; Calcium supplement; Dietary Supplements; Drug toxicity and drugs side effects treatment; Estrogen; Estrogens, Conjugated (USP) - administration & dosage; Estrogens, Conjugated (USP) - adverse effects; Female; Hormone Replacement Therapy - adverse effects; Humans; Kidney Calculi - chemically induced; Medical sciences; Medrogestone - administration & dosage; Medrogestone - adverse effects; Middle Aged; Nephrolithiasis; Osteoporosis; Osteoporosis, Postmenopausal - prevention & control; Pharmacology. Drug treatments; Risk Assessment; Supersaturation; Toxicity: urogenital system; Osteoporosis; Supersaturation; Calcium oxalate; Nephrolithiasis; Estrogen; Calcium supplement; Kidney disease; Human; Replacement therapy; Urinary system disease; Calcium; Medrogestone; Oxalate; Toxicity; Menopause; Diseases of the osteoarticular system; Bone disease; Kidney; Urinary stone; Progestagen; Calcium carbonate; Lithiasis; Postmenopause; Female; Conjugated compound; Sex steroid hormone
• ISSN: 0378-5122; 1873-4111
• DOI: 10.1016/S0378-5122(01)00277-8

Background: Recent studies showed that postmenopausal women lost less bone mass when supplemented with calcium or estrogen therapy. However, the safety of the treatments in terms of the risk of calcium oxalate stone formation is unknown. We therefore conducted this study to determine the alteration in calcium oxalate supersaturation after calcium supplement or after combined calcium and estrogen therapy in postmenopausal osteoporotic women.
Methods: Fifty-six postmenopausal women were enrolled in this study. All subjects were more than 10 years postmenopausal with vertebral or femoral osteoporosis by bone mineral density criteria. They were randomly allocated to receive either 625 mg of calcium carbonate (250 mg of elemental calcium) at the end of a meal three times a day (group A,
n=26) or calcium carbonate in the same manner plus 0.625 mg/day of conjugated equine estrogen and 5 mg medrogestone acetate from day 1–12 each month (group B,
n=30). The age (mean±S.E.M.) was 66.3±1.2 and 65.1±1.1 years, weight 54.1±1.2 and 55.3±2.1 kg, in group A and group B, respectively. Urine specimens (24-h) were collected at baseline and 3 months after treatment for the determination of calcium oxalate saturation by using Tiselius's index (AP(CaOx)) and calcium/citrate ratio.
Results: After 3 months of treatment, there was no significant alteration from baseline for urinary excretion of calcium, citrate and oxalate. Urinary phosphate excretion was significantly reduced (6.3±0.7 vs. 5.1±0.7 mmol/day for group A and 8.2±0.9 vs. 5.8±0.7 mmol/day for group B,
P<0.05), whereas net alkaline absorption was significantly elevated (10.1±3.6 vs. 20.1±4.4 meq/day for group A and 4.8±3.2 vs. 19.9±3.6 meq/day for group B,
P<0.05). Calcium/citrate ratio and AP(CaOx) determined at baseline were not different from the corresponding values after treatment in both groups; calcium/citrate: 10.1±3.1 vs. 10.1±2.5 for group A and 9.3±1.8 vs. 11.9±2.5 for group B and AP(CaOx): 1.1±0.1 vs. 1.3±0.2 for group A and 1.2±0.2 vs. 1.1±0.1 for group B. There were eight and nine patients with high AP(CaOx), or >2, at baseline and after treatment, respectively.
Conclusions: Calcium supplement with a meal or combined calcium supplement and estrogen therapy is not associated with a significant increased risk of calcium oxalate stone formation in the majority of postmenopausal osteoporotic patients. Determination of urinary saturation for calcium oxalate after calcium and estrogen supplements, especially at the initial phase of treatment, may be helpful in the avoidance of nephrolithiasis.