Clinical profile of patients with renal calculi attending a bone health clinic

Abstract

Idiopathic hypercalciuria is a known association with osteoporosis. We explored characteristics of patients with renal stones attending our clinic. A proportion of patients are expected to have abnormal calcium and phosphate absorption and excretion. A concern in the utilisation of vitamin D and parathyroid hormone (PTH) therapy is the potential to induce renal calculi. We interrogated the database of St. James's Hospital (Dublin) Bone Clinic — a tertiary referral centre for osteoporosis and bone health. It has 3600 patient records spanning 8 years. We identified 29 patients with renal calculi. Some had commenced treatment for osteoporosis before attending. At first presentation, baseline parameters of age, sex, serum 25-OH vitamin D, serum PTH, serum calcium, magnesium and phosphate, creatinine clearance (Cockcroft-Gault) and 24-hour urinary calcium excretion, as well as serum bone markers (osteocalcin, Procollagen type 1 N-terminal propeptide (P1NP), and CTXtelopeptide) and T-scores of spine and hip on DEXA scan were recorded. Our results are as follows: Number of patients n=29 (6 male, 23 female); mean age 70 years (SD 11.7); mean T-score spine −2.93 (SD 2.19), mean T-score hip −2.30 (SD 1.18); mean serum 25-OH vitamin D 43 nmol/L (SD 27); mean serum PTH 47.8 pg/mL (SD 31.9); mean serum calcium 2.32 mmol/L (SD 0.24); mean serum magnesium 0.83 mmol/L (SD 0.10); mean serum phosphate 0.94 mmol/L (SD 0.19); mean creatinine clearance 66 mL/min (SD 28.6); mean serum osteocalcin 25.2 ng/mL (SD 25.03); mean serum P1NP 50.2 ng/mL (SD 57.08); mean serum CTX 0.34 ng/mL (SD 0.51); mean 24-hour urinary calcium excretion 3.48 mmol/24 h (SD 1.80). Notable correlation coefficients were: serum PTH vs. 24-hour urinary calcium excretion −0.29; creatinine clearance vs. T-score hip 0.61; age of patients vs. serum PTH 0.41; age vs. 24-hour urinary calcium excretion −0.34. In conclusion, this is an elderly cohort of patients with vitamin D deficiency and an element of chronic renal failure, but over all bone turnover appeared normal. Ideally, some would be treated with alphacalcidol; however, this is an active metabolite of vitamin D, and should be used cautiously in the context of renal calculi. In contrast, the fact that not a lot of these patients were hypercalciuric is perhaps a result of their underlying vitamin D deficiency. These data will assist us in making rational therapeutic decisions in optimal therapeutic options for this complicated patient group. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.518 PP389-M ZP2307, a novel cyclic PTH(1–17) analog, reverses established osteopenia in adult ovariectomized rats J. Vaaraniemi ⁎, J. Morko , Z.Q. Peng , J.P. Rissanen , M.I. Suominen , K.M. Fagerlund , T.A. Suutari , H.C.M. Boonen , T.S.R. Neerup , H.H. Bak , J.M. Halleen a a Pharmatest Services Ltd, Turku, Finland b Department of Pharmacology and Pharmacotherapy, University of Copenhagen, Copenhagen, Denmark c Zealand Pharma A/S, Glostrup, Denmark Abstract: Recombinant human parathyroid hormone (PTH) analogs (1–34) and (1–84) are used as bone anabolic agents in clinical practice. Hitherto, PTH analogs shorter than 28 amino acids have not demonstrated any bone anabolic activity in vivo. Recently, Zealand Pharma A/S has developed a novel, cyclic PTH(1–17) analog, ZP2307, with a high efficacy and potency on the human PTH receptor in vitro. This study characterized the effects of Recombinant human parathyroid hormone (PTH) analogs (1–34) and (1–84) are used as bone anabolic agents in clinical practice. Hitherto, PTH analogs shorter than 28 amino acids have not demonstrated any bone anabolic activity in vivo. Recently, Zealand Pharma A/S has developed a novel, cyclic PTH(1–17) analog, ZP2307, with a high efficacy and potency on the human PTH receptor in vitro. This study characterized the effects of intermittent treatment with ZP2307 on established osteopenia in adult ovariectomized (OVX) rats. Female Sprague–Dawley rats were ovariectomized at 6 months of age. After 6 weeks without treatment, a reduction in trabecular bone mineral density (Tb.BMD) was confirmed by peripheral quantitative computed tomography (pQCT) in tibial metaphysis of OVX rats. Treatment was started at 7 weeks after the operations and continued once daily for 6 weeks. The osteopenic rats were treated subcutaneously with ZP2307 at 2, 6, 20, 60 and 200 μg/kg/d and with PTH(1–34) at 1.2, 4, 12, 40 and 120 μg/kg/d. Treatment effects were analyzed by pQCT, bone histomorphometry and biomechanical testing in long bones and lumbar spine. During the treatment period, Tb.BMD decreased in tibial metaphysis of OVX rats treated with vehicle. Treatment with ZP2307 reversed the OVX-induced reduction in Tb. BMD and bone volume (BV/TV) in tibial metaphysis and lumbar vertebra at all doses in a dose-dependent manner. ZP2307 enhanced an OVX-induced increase in bone formation rate (BFR/BS) at 200 μg/kg/d and reversed an OVX-induced increase in the number of osteoclasts (N.Oc/B.Pm) at 2–200 μg/kg/d. As a functional consequence in lumbar vertebra, ZP2307 reversed an OVX-induced reduction in maximal load at 6–200 μg/kg/d and increased modulus at 20–200 μg/kg/d. Furthermore, ZP2307 increased cortical thickness and enhanced endocortical BFR/BS in tibial diaphysis at 60–200 μg/kg/d. Treatment with PTH(1–34) induced similar dose-dependent effects although stronger than ZP2307. ZP2307 exhibited 51% efficacy and 1.4-fold potency in tibial metaphysis and 92% efficacy and 3.4-fold potency in lumbar vertebra compared to PTH(1–34). This study demonstrated that the intermittent treatment with ZP2307, the novel cyclic PTH(1–17) analog, is effective in reversing the established osteopenia in adult OVX rats to normal conditions. Due to its broad dose response relationship, ZP2307 may have a wider therapeutic window and a better safety/ efficacy profile than the PTH analogs used in clinical practice. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: J. Vaaraniemi Employee of Pharmatest Services Ltd, J. Morko Employee of Pharmatest Services Ltd, Z. Peng Employee of Pharmatest Services Ltd, J. Rissanen Shareholder of Pharmatest Services Ltd, Employee of Pharmatest Services Ltd, M. Suominen Shareholder of Pharmatest Services Ltd, Employee of Pharmatest Services Ltd, K. Fagerlund Shareholder of Pharmatest Services Ltd, Employee of Pharmatest Services Ltd, T. Suutari Employee of Pharmatest Services Ltd, H. Boonen: None declared, T. Neerup Employee of Zealand Pharma A/S, H. Bak Employee of Zealand Pharma A/S, J. Halleen Shareholder of Pharmatest Services Ltd, Employee of Pharmatest Services Ltd. doi:10.1016/j.bone.2011.03.519 PP390-T Results of two years therapy with strontium ranelate on bone mass and geometry in postmenopausal osteoporotic women. A peripheral quantitative computed tomography (pQCT) study K. Stathopoulos ⁎, P. Katsimbri, E. Atsali, G. Kiniklis, A.B. Zoubos, G. Skarantavos Bone Metabolic Unit, 1st Orthopedic University Clinic, Attikon Hospital, Athens, Greece Abstract: Aims: We assessed the effects of strontium ranelate on bone mass, volumetric densities and geometrical properties of bone in postmenopausal osteoporotic women using tibia pQCT. Methods: We reviewed records of 32 postmenopausal women who received strontium ranelate per os daily for 2 consecutive years. Inclusion criteria: 1) age >50 y, Aims: We assessed the effects of strontium ranelate on bone mass, volumetric densities and geometrical properties of bone in postmenopausal osteoporotic women using tibia pQCT. Methods: We reviewed records of 32 postmenopausal women who received strontium ranelate per os daily for 2 consecutive years. Inclusion criteria: 1) age >50 y, 2) postmenopausal status >2 y, 3) DXA measurement (Spine/Hip) with T score <−2.5 SD, and 4) Tibia pQCT before, 1 y and 2 y after treatment. Exclusion criteria: 1) Secondary osteoporosis' conditions, 2) Other bone metabolic diseases, 3) Previous use of bone anabolic agents, and 4) malignancies. Patients had tibia pQCT (StratecMedizintechnik, Pforzheim, Germany), 3 slices were obtained at the 4% (trabecular), 14% (subcortical and cortical) and 38% (cortical bone) of tibia length sites. We studied 15 variables per slice, mainly total bone content (TOT_CNT), total density (TOT_DEN), trabecular content (TRB_CNT), trabecular density (TRB_DEN), cortical content (CRT_CNT), cortical density (CRT_DEN), subcortical content (CRTSUB_CNT), subcortical density (CRTSUB_DEN), cortical area (CRT_A), subcortical area (CRTSUB_A), mean cortical thickness (CRT_THK), and Stress Strength Indexes (SSIs) at the 14% and 38% sites. Results were corrected for strontium ranelate atomic weight. We performed statistical analysis (t-test, ANCOVA)— data expressed asmean±standard deviation (S.D.).Results: Patients' mean agewas 64.3±12.6 y and mean tibia length 352.14±65.03 mm. After 2 years treatment, we report increases at the 14% site in ΤΟΤ_CNT (181.04±21.51 vs 183.05±21.34, p=0.006), SUBCRT_CNT (168.64±19.58 vs 170.48±19.11, p=0.005), and CRT_CNT (62.91±18.58 vs 66.63±20.63, p=0.021). At the 38% site we report increases in TOT_CNT (276.46±36.24 vs 278.94±35.71, p=0.09), SUBCRT_CNT (205.86±25.60 vs 208.59±25.47, p<0.000), CRT_CNT (160.09±31.19 vs 168.84±32.62, p<0.000) and CRT_DEN (1192.46±14.50 vs 1203.15±17.05, p<0.000). We also report increases in CRT_A (134.18±25.73 vs 140.13±26.57, p<0.000) and mean CRT_THK (2.18±0.44 vs 2.28±0.46, p=0.001). Conclusions: Our results indicate that 2 years therapy with strontium ranelate increase significantly bone mass, volumetric cortical densities, cortical area and mean cortical thickness in postmenopausal osteoporotic women. Abstracts / Bone 48 (2011) S213–S235 S222