Osteoporosis International

, Volume 25, Issue 6, pp 1717–1726 | Cite as

Effects of PTH(1–84) therapy on muscle function and quality of life in hypoparathyroidism: results from a randomized controlled trial

  • T. Sikjaer
  • L. Rolighed
  • A. Hess
  • A. Fuglsang-Frederiksen
  • L. Mosekilde
  • L. Rejnmark
Original Article

Abstract

Summary

The effects of treatment with 100 μg parathyroid hormone (PTH) (1–84) or an identical placebo on muscle function and quality of life (QoL) was studied in hypoparathyroid patients. At baseline, we found reduced QoL but no myopathy in the patients. Six months of treatment did not improve QoL, and muscle strength decreased slightly.

Introduction

A reduced quality of life (QoL) and myopathy that may be due to the absence of PTH have been reported in patients with hypoparathyroidism (hypoPT).

Methods

Sixty-two patients with chronic hypoPT were randomized to 6 months of treatment with either PTH(1–84) 100 μg/d s.c. or placebo, given as add-on therapy to conventional treatment. Muscle function and postural stability were investigated using a dynamometer chair, a stadiometer platform, the repeated chair stands test, the timed up and go test, and electromyography. QoL was assessed using the 36-item Short Form Health Survey and the WHO-5 Well-Being Index.

Results

The mean age of the patients was 52 ± 11 years, and 85 % were females. At baseline, QoL was significantly reduced in comparison with norm-based scores. Compared with placebo, PTH did not improve QoL or muscle function. Rather, max force production decreased significantly by 30 % at elbow flexion in the PTH group compared with the placebo group. Moreover, there was a nonsignificant trend for muscle strength to decrease in the upper extremities and on knee extension in response to PTH. Treatment did not affect postural stability. Electromyography showed a slight decrease in the duration of motor unit potentials in the PTH group, indicating a tendency toward myopathy, which, however was not symptomatic.

Conclusions

Overall, our data do not support an immediate beneficial effect of PTH replacement therapy on muscle function or QoL. A high frequency of hypercalcemia among our patients may have compromised the potential beneficial effects of reversing the state of PTH insufficiency.

Keywords

Hypoparathyroidism Muscle function Quality of life rhPTH(1–84) 

References

  1. 1.
    Abe S, Tojo K, Ichida K, Shigematsu T, Hasegawa T, Morita M, Sakai O (1996) A rare case of idiopathic hypoparathyroidism with varied neurological manifestations. Intern Med 35:129–134PubMedCrossRefGoogle Scholar
  2. 2.
    Nora DB, Fricke D, Becker J, Gomes I (2004) Hypocalcemic myopathy without tetany due to idiopathic hypoparathyroidism: case report. Arq Neuropsiquiatr 62:154–157PubMedCrossRefGoogle Scholar
  3. 3.
    Shane E, McClane KA, Olarte MR, Bilezikian JP (1980) Hypoparathyroidism and elevated muscle enzymes. Neurology 30:192–195PubMedCrossRefGoogle Scholar
  4. 4.
    Snowdon JA, Macfie AC, Pearce JB (1976) Hypocalcaemic myopathy with paranoid psychosis. J Neurol Neurosurg Psychiatry 39:48–52PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Syriou V, Kolitsa A, Pantazi L, Pikazis D (2005) Hypoparathyroidism in a patient presenting with severe myopathy and skin rash. Case report and review of the literature. Hormones (Athens) 4:161–64Google Scholar
  6. 6.
    Van Offel JF, De Gendt CM, De Clerck LS, Stevens WJ (2000) High bone mass and hypocalcaemic myopathy in a patient with idiopathic hypoparathyroidism. Clin Rheumatol 19:64–66PubMedGoogle Scholar
  7. 7.
    Walters RO (1979) Idiopathic hypoparathyroidism with extrapyramidal and myopathic features. Arch Dis Child 54:236–238PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Arlt W, Fremerey C, Callies F, Reincke M, Schneider P, Timmermann W, Allolio B (2002) Well-being, mood and calcium homeostasis in patients with hypoparathyroidism receiving standard treatment with calcium and vitamin D. Eur J Endocrinol 146:215–222PubMedCrossRefGoogle Scholar
  9. 9.
    Bohrer T, Krannich JH (2007) Depression as a manifestation of latent chronic hypoparathyroidism. World J Biol Psychiatry 8:56–59PubMedCrossRefGoogle Scholar
  10. 10.
    Lawlor BA (1988) Hypocalcemia, hypoparathyroidism, and organic anxiety syndrome. J Clin Psychiatry 49:317–318PubMedGoogle Scholar
  11. 11.
    Velasco PJ, Manshadi M, Breen K, Lippmann S (1999) Psychiatric aspects of parathyroid disease. Psychosomatics 40:486–490PubMedCrossRefGoogle Scholar
  12. 12.
    Yamaguchi H, Okamoto K, Shooji M, Morimatsu M, Hirai S (1987) Muscle histology of hypocalcaemic myopathy in hypoparathyroidism. J Neurol Neurosurg Psychiatry 50:817–818PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Winer KK, Ko CW, Reynolds JC, Dowdy K, Keil M, Peterson D, Gerber LH, McGarvey C, Cutler GB Jr (2003) Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1–34) versus calcitriol and calcium. J Clin Endocrinol Metab 88:4214–4220PubMedCrossRefGoogle Scholar
  14. 14.
    Cusano NE, Rubin MR, McMahon DJ, Irani D, Tulley A, Sliney J Jr, Bilezikian JP (2013) The Effect of PTH(1–84) on quality of life in hypoparathyroidism. J Clin Endocrinol Metab 98:2356–2361PubMedCrossRefGoogle Scholar
  15. 15.
    Reppe S, Stilgren L, Abrahamsen B, Olstad OK, Cero F, Brixen K, Nissen-Meyer LS, Gautvik KM (2007) Abnormal muscle and hematopoietic gene expression may be important for clinical morbidity in primary hyperparathyroidism. Am J Physiol Endocrinol Metab 292:E1465–E1473PubMedCrossRefGoogle Scholar
  16. 16.
    Hoare SR, Usdin TB (2001) Molecular mechanisms of ligand recognition by parathyroid hormone 1 (PTH1) and PTH2 receptors. Curr Pharm Des 7:689–713PubMedCrossRefGoogle Scholar
  17. 17.
    Smock SL, Vogt GA, Castleberry TA, Lu B, Owen TA (2001) Molecular cloning and functional characterization of the canine parathyroid hormone/parathyroid hormone related peptide receptor (PTH1). Mol Biol Rep 28:235–243PubMedCrossRefGoogle Scholar
  18. 18.
    Sikjaer T, Rejnmark L, Rolighed L, Heickendorff L, Mosekilde L (2011) The effect of adding PTH(1–84) to conventional treatment of hypoparathyroidism: a randomized, placebo-controlled study. J Bone Miner Res 26:2358–2370PubMedCrossRefGoogle Scholar
  19. 19.
    Tiainen K, Sipila S, Kauppinen M, Kaprio J, Rantanen T (2009) Genetic and environmental effects on isometric muscle strength and leg extensor power followed up for three years among older female twins. J Appl Physiol 106:1604–1610PubMedCrossRefGoogle Scholar
  20. 20.
    Rantanen T, Era P, Heikkinen E (1996) Maximal isometric knee extension strength and stair-mounting ability in 75- and 80-year-old men and women. Scand J Rehabil Med 28:89–93PubMedGoogle Scholar
  21. 21.
    Csuka M, McCarty DJ (1985) Simple method for measurement of lower extremity muscle strength. Am J Med 78:77–81PubMedCrossRefGoogle Scholar
  22. 22.
    Podsiadlo D, Richardson S (1991) The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 39:142–148PubMedGoogle Scholar
  23. 23.
    Thrane G, Joakimsen RM, Thornquist E (2007) The association between timed up and go test and history of falls: the Tromso study. BMC Geriatr 7:1PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Steffen TM, Hacker TA, Mollinger L (2002) Age- and gender-related test performance in community-dwelling elderly people: six-minute walk test, Berg balance scale, timed up & go test, and gait speeds. Phys Ther 82:128–137PubMedGoogle Scholar
  25. 25.
    Ceria-Ulep CD, Grove J, Chen R, Masaki KH, Rodriguez BL, Donlon TA, Guralnik J, Willcox BJ, Willcox DC, Nigg C, Curb JD (2010) Physical aspects of healthy aging: assessments of three measures of balance for studies in middle-aged and older adults. Curr Gerontol Geriatr Res 2010:849761PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Era P, Sainio P, Koskinen S, Haavisto P, Vaara M, Aromaa A (2006) Postural balance in a random sample of 7,979 subjects aged 30 years and over. Gerontology 52:204–213PubMedCrossRefGoogle Scholar
  27. 27.
    Fuglsang-Frederiksen A (2006) The role of different EMG methods in evaluating myopathy. Clin Neurophysiol 117:1173–1189PubMedCrossRefGoogle Scholar
  28. 28.
    Fuglsang-Frederiksen A, Lo MM, Dahl K (1985) Turns analysis (peak ratio) in EMG using the mean amplitude as a substitute of force measurement. Electroencephalogr Clin Neurophysiol 60:225–227PubMedCrossRefGoogle Scholar
  29. 29.
    Liguori R, Dahl K, Fuglsang-Frederiksen A, Trojaborg W (1992) Turns-amplitude analysis of the electromyographic recruitment pattern disregarding force measurement. II. Findings in patients with neuromuscular disorders. Muscle Nerve 15:1319–1324PubMedCrossRefGoogle Scholar
  30. 30.
    Fuglsang-Frederiksen A, Mansson A (1975) Analysis of electrical activity of normal muscle in man at different degrees of voluntary effort. J Neurol Neurosurg Psychiatry 38:683–694PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Buchthal F, Kamieniecka Z (1982) The diagnostic yield of quantified electromyography and quantified muscle biopsy in neuromuscular disorders. Muscle Nerve 5:265–280PubMedCrossRefGoogle Scholar
  32. 32.
    Ware JE, Kosinski M, Gandek B (2005) SF-36 Health survey. Manual and interpretation guideGoogle Scholar
  33. 33.
    Ware JE, Kosinski M, Bjoerner J, Turner-Bowker DM, Gandek B, Maruish ME (2007) Scoring procedures. 2nd edn. 53–64Google Scholar
  34. 34.
    de Wit M, Pouwer F, Gemke RJBJ, Delemarre-van de Waal H, Snoek FJ (2007) Validation of the WHO-5 Well-Being Index in adolescents with type 1 diabetes. Diabetes Care 30:2003–2006PubMedCrossRefGoogle Scholar
  35. 35.
    Sikjaer T, Rejnmark L, Thomsen JS, Tietze A, Bruel A, Andersen G, Mosekilde L (2012) Changes in 3-dimensional bone structure indices in hypoparathyroid patients treated with PTH(1–84): a randomized controlled study. J Bone Miner Res 27:781–788PubMedCrossRefGoogle Scholar
  36. 36.
    Kaebling R (1962) The psychiatric aspects of hypoparathyroidism. Acta Psychiatr Scand Suppl 38:1–70Google Scholar
  37. 37.
    Lajeunesse C, Everett J, Laplante L, Villeneuve A, Cote R, Thomas J (1989) Neuropsychology of a psycho-organic syndrome caused by idiopathic hypoparathyroidism. Apropos of a case. Encéphale 15:295–298PubMedGoogle Scholar
  38. 38.
    Divieti P, Inomata N, Chapin K, Singh R, Juppner H, Bringhurst FR (2001) Receptors for the carboxyl-terminal region of PTH(1–84) are highly expressed in osteocytic cells. Endocrinology 142:916–925PubMedGoogle Scholar
  39. 39.
    Usdin TB, Bonner TI, Hoare SR (2002) The parathyroid hormone 2 (PTH2) receptor. Recept Channels 8:211–218PubMedCrossRefGoogle Scholar
  40. 40.
    Sikjaer T, Amstrup AK, Rolighed L, Kjaer SG, Mosekilde L, Rejnmark L (2013) PTH (1–84) Replacement therapy in hypoparathyroidism: a randomized controlled trial on pharmacokinetic and dynamic effects following 6 months of treatment. J Bone Miner Res; n/aGoogle Scholar
  41. 41.
    Ware JE, Kosinski M, Bjoerner J, Turner-Bowker DM, Gandek B, Maruish ME (2007) SF-36v2 Health survey standard form disease-specific norms. 2nd ednGoogle Scholar
  42. 42.
    Winer KK, Yanovski JA, Sarani B, Cutler GB Jr (1998) A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1–34 in treatment of hypoparathyroidism. J Clin Endocrinol Metab 83:3480–3486PubMedGoogle Scholar
  43. 43.
    Winer KK, Sinaii N, Peterson D, Sainz B Jr, Cutler GB Jr (2008) Effects of once versus twice-daily parathyroid hormone 1–34 therapy in children with hypoparathyroidism. J Clin Endocrinol Metab 93:3389–3395PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Winer KK, Zhang B, Shrader JA, Peterson D, Smith M, Albert PS, Cutler GB Jr (2012) Synthetic human parathyroid hormone 1–34 replacement therapy: a randomized crossover trial comparing pump versus injections in the treatment of chronic hypoparathyroidism. J Clin Endocrinol Metab 97:391–399PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2014

Authors and Affiliations

  • T. Sikjaer
    • 1
  • L. Rolighed
    • 2
  • A. Hess
    • 3
  • A. Fuglsang-Frederiksen
    • 3
  • L. Mosekilde
    • 1
  • L. Rejnmark
    • 1
  1. 1.Osteoporosis Clinic, Department of Internal Medicine and Endocrinology, MEAAarhus University HospitalAarhusDenmark
  2. 2.Department of Surgery PAarhus University HospitalAarhusDenmark
  3. 3.Department of Clinical NeurophysiologyAarhus University HospitalAarhusDenmark

Personalised recommendations