Osteoporosis International

, Volume 18, Issue 1, pp 59–68

Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment

  • P. D. Miller
  • E. N. Schwartz
  • P. Chen
  • D. A. Misurski
  • J. H. Krege
Original Article

Abstract

Introduction

The prevalence of both osteoporosis and renal impairment increases with age.

Methods

Using data from the Fracture Prevention Trial, the safety and efficacy of teriparatide [rhPTH(1–34)] in postmenopausal women with osteoporosis and renal impairment were explored. Patients were required to have serum creatinine concentrations ≤2.0 mg/dl and normal serum parathyroid hormone (PTH) concentrations and were randomized to receive daily subcutaneous injections of placebo or teriparatide 20 or 40 mcg/day. Glomerular filtration rate (GFR) was estimated using the Cockcroft–Gault equation. Patients were defined from baseline assessments to have normal (GFR ≥80 ml/min), mildly impaired (GFR 50–79 ml/min), or moderately impaired (GFR 30–49 ml/min) renal function for bone mineral density (BMD) and amino-terminal extension peptide of procollagen type 1 (PINP) analyses, and normal (GFR ≥80 ml/min) or impaired (GFR <80 ml/min) renal function for fracture analyses.

Results and conclusions

Compared with patients with normal renal function, patients with renal impairment were older, shorter, weighed less, had been postmenopausal longer, and had lower baseline lumbar spine and femoral neck BMD. Compared with placebo, teriparatide significantly increased PINP and lumbar spine and femoral neck BMD within each renal function subgroup, and there was no evidence that these increases were altered by renal insufficiency (each treatment-by-subgroup interaction p>0.05). Similarly, teriparatide-mediated vertebral and nonvertebral fracture risk reductions were similar and did not differ significantly between patients with normal or impaired renal function (treatment-by-subgroup interactions p>0.05). The incidences of treatment-emergent and renal-related adverse events were consistent across treatment assignment in the normal, mildly impaired, and moderately impaired renal function subgroups. Teriparatide induced changes in mean GFR were unaffected by baseline renal function (treatment-by-renal function interaction p>0.05 for normal, mildly impaired, or moderately impaired subgroups). Patients in all renal function categories treated with teriparatide 20 or 40 mcg had an increased incidence of 4–6-h postdose serum calcium >10.6 mg/dl (the upper limit of normal) versus placebo; however, teriparatide 20 mcg/day was not associated with significantly increased incidence of 4–6-h postdose serum calcium >11 mg/dl in any renal function category.

Teriparatide therapy was associated with increased incidence of elevated uric acid, with the incidences being highest in patients with moderately impaired renal function and in those receiving teriparatide 40 mcg/day. Even so, adverse event data did not suggest an increased incidence of gout or arthralgia or of nephrolithiasis events in teriparatide-treated patients with normal, mild, or moderate renal impairment.

Keywords

Adverse events Bone mineral density Fragility fracture Osteoporosis Renal impairment Teriparatide 

References

  1. 1.
    NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795CrossRefGoogle Scholar
  2. 2.
    Looker AC, Johnston CC Jr, Wahner HW, Dunn WL, Calvo MS, Harris TB et al (1995) Prevalence of low femoral bone density in older U.S. women from NHANES III. J Bone Miner Res 10:796–802PubMedGoogle Scholar
  3. 3.
    Looker AC, Orwoll ES, Johnston CC Jr, Lindsay RL, Wahner HW, Dunn WL et al (1997) Prevalence of low femoral bone density in older U.S. adults from NHANES III. J Bone Miner Res 12:1761–1768PubMedCrossRefGoogle Scholar
  4. 4.
    Jones CA, McQuillan GM, Kusek JW, Eberhardt MS, Herman WH, Coresh J et al (1998) Serum creatinine levels in the US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis 32:992–999PubMedCrossRefGoogle Scholar
  5. 5.
    Klawansky S, Komaroff E, Cavanaugh PF Jr, Mitchell DY, Gordon MJ, Connelly JE et al (2003) Relationship between age, renal function and bone mineral density in the US population. Osteoporos Int 14:570–576PubMedCrossRefGoogle Scholar
  6. 6.
    Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY et al (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRefGoogle Scholar
  7. 7.
    Lu Y, Ye K, Mathur AK, Hui S, Fuerst TP, Genant HK (1997) Comparative calibration without a gold standard. Stat Med 16:1889–1905PubMedCrossRefGoogle Scholar
  8. 8.
    Lu Y, Mathur AK, Blunt BA, Gluer CC, Will AS, Fuerst TP et al (1996) Dual X-ray absorptiometry quality control: comparison of visual examination and process-control charts. J Bone Miner Res 11:626–637PubMedGoogle Scholar
  9. 9.
    Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148PubMedGoogle Scholar
  10. 10.
    Chen P, Satterwhite JH, Licata AA, Lewiecki EM, Sipos AA, Misurski DM et al (2005) Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis. J Bone Miner Res 20:962–970PubMedCrossRefGoogle Scholar
  11. 11.
    Eastell R, Chen P, Krege JH (2005) Monitoring teriparatide therapy for osteoporosis with procollagen type I N-Propeptide (PINP). Curr Med Res Opin 22(1):61–68CrossRefGoogle Scholar
  12. 12.
    Miller PD, Roux C, Boonen S, Barton IP, Dunlap LE, Burgio DE (2005) Safety and efficacy of oral risedronate in patients with reduced renal function as assessed by the Cockcroft-Gault method: a pooled analysis from 9 clinical trials. J Bone Miner Res 20:2105–2115PubMedCrossRefGoogle Scholar
  13. 13.
    Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41PubMedCrossRefGoogle Scholar
  14. 14.
    Food and Drug Administration, U. S. Department of Health and Human Services (1998) Guidance for industry. Pharmacokinetics in patients with impaired renal function-study design, data analysis, and impact on dosing and labeling. Available at http://www.fda.gov/cder/guidance/1449.pdf. Accessed May 31, 2005
  15. 15.
    Lindeman RD (1993) Assessment of renal function in the old. Special considerations. Clin Lab Med 13:269–277PubMedGoogle Scholar
  16. 16.
    Ensrud KE, Palermo L, Black DM, Cauley J, Jergas M, Orwoll ES et al (1995) Hip and calcaneal bone loss increase with advancing age: longitudinal results from the study of osteoporotic fractures. J Bone Miner Res 10:1778–1787PubMedCrossRefGoogle Scholar
  17. 17.
    Krege JH, Donley DW, Marcus R (2005) Teriparatide, osteoporosis, calcium, and vitamin D. N Engl J Med 353:634–635PubMedCrossRefGoogle Scholar
  18. 18.
    US Forteo Prescribing Information (2004) Eli Lilly and Company, Indianapolis, IN, USAGoogle Scholar
  19. 19.
    Miller PD, Bilezikian JP, Deal C, Harris ST, Pacifici R (2004) Clinical use of teriparatide in the real world: initial insights. Endocr Pract 10:139–148PubMedGoogle Scholar
  20. 20.
    Massry SG, Coburn JW, Lee DB, Jowsey J, Kleeman CR (1973) Skeletal resistance to parathyroid hormone in renal failure. Studies in 105 human subjects. Ann Intern Med 78:357–364PubMedGoogle Scholar
  21. 21.
    Llach F, Massry SG, Singer FR, Kurokawa K, Kaye JH, Coburn JW (1975) Skeletal resistance to endogenous parathyroid hormone in patients with early renal failure. A possible cause for secondary hyperparathyroidism. J Clin Endocrinol Metab 41:339–345PubMedCrossRefGoogle Scholar
  22. 22.
    US Fosamax Prescribing Information (2004) Merck and Co., Whitehouse Station, NJ, USAGoogle Scholar
  23. 23.
    US Actonel Prescribing Information (2004) Procter & Gamble Pharmaceuticals, Cincinnati, USAGoogle Scholar
  24. 24.
    US Zometa Prescribing Information (2005) Novartis Pharmaceuticals, East Hanover, NJ, USAGoogle Scholar
  25. 25.
    Lin J, Knight EL, Hogan ML, Singh AK (2003) A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease. J Am Soc Nephrol 14:2573–2580PubMedCrossRefGoogle Scholar
  26. 26.
    Garg AX, Papaioannou A, Ferko N, Campbell G, Clarke JA, Ray JG (2004) Estimating the prevalence of renal insufficiency in seniors requiring long-term care. Kidney Int 65:649–653PubMedCrossRefGoogle Scholar
  27. 27.
    Lafayette RA, Perrone RD, Levey AS (1993) Laboratory evaluation of renal function. In: Schrier RW, Gottschalk CW (eds) Diseases of the kidney. Little, Brown and Company, Boston/Toronto/London, pp 333–370Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  • P. D. Miller
    • 1
  • E. N. Schwartz
    • 2
  • P. Chen
    • 3
  • D. A. Misurski
    • 3
  • J. H. Krege
    • 3
  1. 1.Department of MedicineUniversity of Colorado Health Sciences Center & Colorado Center for Bone ResearchDenverUSA
  2. 2.Northern California Institute for Bone HealthOaklandUSA
  3. 3.Lilly Research LaboratoriesEli Lilly and CompanyIndianapolisUSA

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