Effects of 6 months strontium ranelate administration on phosphocalcium metabolism in postmenopausal women with reduced bone density
AA Joshi1, AM Ahmad1, P Whittingham1, V Gupta1, A Hamilton1, BH Durham2, WD Fraser2 & JP Vora1
Introduction: Strontium ranelate (SR) is a dual action bone agent that increases bone formation and reduces bone resorption. Previous long term studies with SR have demonstrated minimal reductions in parathyroid hormone (PTH) and adjusted calcium (ACa) levels with increase in phosphate (PO4) concentrations, but the exact mechanism of action of SR remains unclear. Postmenopausal women with low bone mineral density (BMD) have relatively high circulating PTH concentrations, abnormal PTH circadian rhythm, abnormal phosphocalcium metabolism, and may be insensitive to the effects of PTH. We studied the effects of SR on PTH sensitivity and phosphocalcium metabolism at baseline and 1, 3 and 6 months after therapy.
Methods: Eight postmenopausal women with low BMD (average age 64±3.1 years (Mean±S.E.M.); T-score: lumbar spine (L2L4)=−1.97±0.2, femoral neck=−1.58±0.2) were commenced on 2 g of SR/day. Patients were hospitalized for 24 h prior to and 1, 3 and 6 months after SR administration. Half-hourly blood and 3-hourly urine samples were collected for PTH, ACa, PO4 and nephrogenous cyclic-AMP (NcAMP-index of PTH activity at the level of kidneys).
Results: Twenty-four hour mean PTH concentration decreased following 1 (4.31±0.05 pmol/l), 3 (4.30±0.05 pmol/l) and 6 (4.10±0.06 pmol/l) months of SR administration compared to baseline (4.60±0.04 pmol/l, P<0.005) and the NcAMP remained unchanged at 6 months (12.41±2.13 nmol/l GFR) as compared to baseline (15.44±1.85 nmol/l GFR, P=1.00). Aca decreased at 1 (2.34±0.003 mmol/l) and 6 months (2.26±0.002 mmol/l) as compared to baseline (2.28±0.005 mmol/l, P<0.005) and PO4 concentration increased at 6 months (1.37±0.009 mmol/l) from baseline (1.20±0.008 mmol/l, P<0.005). There was no significant change in Urinary calcium and urinary phosphate excretion.
Discussion: In this study, PTH concentration and mean Aca levels decreased along with an increase in PO4 concentration. The NcAMP remained relatively unchanged, which may suggest an improvement in PTH sensitivity and may explain previously shown improved bone metabolism and BMD with SR.