Skip to main content
Log in

Results of a stimulatory therapy of low bone metabolism in osteoporosis with (1–38)hPTH and diphosphonate EHDP

Protocol of study I, osteoporosis trial Hannover

  • Originalien
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

In contrast to prevention, the therapy of manifest osteoporosis remains a clinically significant problem. So far all therapeutic attempts have yielded unsatisfying results. For this reason we have tried to achieve a positive bone balance by sequential stimulation and inhibition of the osseous metabolism. The therapy consisted of six 14-day courses with 400 units (1–38)hPTH per day and, in addition, starting with the 2nd week of PTH therapy, EHDP 5 mg per kg body weight per day for a total of 2 weeks. Already the initial therapeutic course resulted in a stimulation of decreased bone metabolism which could be documented by an increase in the calcium-47 accretion rate (six patients). An increase of the alkaline phosphatase could be noted (four patients); this, however, did not correlate with the calcium accretion. A positive calcium balance could, nonetheless, only be attained in four of eight patients within this period, while neither the alkaline phosphatase nor the kinetics would allow a prediction of this effect. Changes of the balance coincided with equal changes in the net calcium absorption. The urinary calcium excretion increased temporarily during the therapeutic phase. We were not able to detect an influence on the vitamin D metabolites. Histomorphometric studies did not demonstrate an increase in bone mass in the iliac creast after six therapeutic courses. Nevertheless, progressive deformations of vertebral bodies did not occur. We conclude that already after 2 weeks this therapeutic concept can lead to a stimulation of bone metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AP:

Alkaline phosphatase

BMU:

Basic metabolic unit

cAMP:

Cyclic adenosine monophosphate

EHDP:

Ethidronate (DIPHOS)

NaF:

Sodium-fluoride

NIBSC:

National Institute for Biological Standards and Controls

PTH:

Parathyroid hormone

References

  1. Atkinson MJ, Niepel B, Jüppner H, Casaretto M, Zahn H, Hehrmann R, Hesch RD (1981) A homologous midregional radoiimmunoassay for PTH. J Endocrinol Invest 4:363–366

    Google Scholar 

  2. Atkinson MJ, Schettler T, Bodenstein H, Hesch RD (1984) Osteoporosis: a bone turnover defect resulting from an elevated parathyroid hormone concentration within the bone-marrow cavity? Klin Wochenschr 62:129–132

    Google Scholar 

  3. Calvo MS, Fryer MJ, Laakso KJ, Nissenson RA, Price PA, Murray TM, Health III H (1985) Structural requirements for parathyroid hormone action in mature bone. Effects on release of cyclic adenosine monophosphate and bone gamma-carboxyglutamic acid containing protein from perfused rat hindquarters. J Clin Invest 76:2348–2354

    Google Scholar 

  4. Dambacher MA, Ittner J, Ruegsegger P (1986) Long-term fluoride therapy of postmenopausal osteoporosis. Bone 7(3):199–205

    Google Scholar 

  5. Farley JR, Wergedal JE, Baylink DJ (1983) Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone-forming cells. Science 222:330–332

    Google Scholar 

  6. Frost HM (1979) Treatment of osteoporoses by manipulation of coherent bone cell populations. Clin Orth Rel Res 143:227–244

    Google Scholar 

  7. Frost HM (1984) The ADFR concept revisited. Calcif Tissue Int 36:349

    Google Scholar 

  8. Frost HM (1985) The pathomechanics of osteoporoses. Clin Orthop Rel Res 200:198–225

    Google Scholar 

  9. Gunness-Hey M, Hock JM (1984) Increased trabecular bone mass in rats treated with human synthetic parathyroid hormone. Metab Bone Dis Rel Res 5:177–181

    Google Scholar 

  10. Hefti E, Trechsel U, Bonjour JP, Fleisch H, Schenk R (1982) Increase of whole-body calcium and skeletal mass in normal and osteoporotic adult rats treated with parathyroid hormone. Clin Sci 62:389–396

    Google Scholar 

  11. Hesch RD, Heck J, Schettler T (1985) (1–38) Human parathyroid hormone for coherence therapy of osteoporosis. Acta Endocrinol [Suppl 267] 108:171–172

    Google Scholar 

  12. Keck E, v Lilienfeld-Toal H, Krüskemper HL (1981) Protein binding assays for 25-hydroxy, 24,25-dihydroxy and 1,25-dihydroxy metabolites of vitamin D in human plasma. J Clin Chem Biochem 19:1043

    Google Scholar 

  13. Kleerekoper M, Parfitt AM, Ellis Bl (1984) Measurement of vertebral fracture rates in osteoporosis. Proceedings of the Copenhagen Intern Symposium on Osteoporosis: 103–109

  14. Mazzuoli GF, Passeri M, Gennari C, Minisola S, Antonelli R, Yaltorta C, Palummeri E, Cervellin GF, Gonelli S, Francini G (1986) Effects of salmon calcitonin in postmenopausal osteoporosis: a controlled double-blind clinical study. Calcif Tissue Int 38:3–8

    Google Scholar 

  15. Parsons JA, Robinson CJ (1968) A rapid indirect hypercalcemic action of parathyroid hormone demonstrated in isolated blood perfused bone. In: Talmage RV, Belanger LF (eds) Parathyroid hormone and thyrocalcitonin (calcitonin). Excerpta Medica, Amsterdam, pp 329–331

    Google Scholar 

  16. Parsons JA, Meunier P, Podbesek R, Reeve J, Stevenson RW (1981) Pathological and therapeutic implications of the cellular and humoral responses to parathyrin. Biochem Soc Trans 9:383–386

    Google Scholar 

  17. Podbesek RD, Stevenson R, Zanelli GD, Edouard C, Meunier PJ, Reeve J, Parsons JA (1981) Treatment with human parathyroid hormone fragment (hPTH 1–34) stimulates bone formation and intestinal calcium absorption in the greyhound: comparison with data from the osteoporosis trial. Int Congress Series Exc Medica 511:118–123

    Google Scholar 

  18. Reeve J, Wooton R, Hesp R (1976) A new method for calculating the accretion rate of bone calcium and some observations on the suitability of strontium-85 as a tracer for bone calcium. Calcif Tissue Res 20:121–135

    Google Scholar 

  19. Reeve J, Hesp R, Williams D, Hulme P, Klenerman L, Zanelli JM, Darby AJ, Tregear GW, Parsons JA (1976) Anabolic effect of low doses of a fragment of human parathyroid hormone on the skeleton in postmenopausal osteoporosis. Lancet I:1035–1038

    Google Scholar 

  20. Reeve J, Meunier PJ, Parsons JA, Bernat M, Bijvoet OLM, Courpron P, Edouard C, Klenerman L, Neer NM, Renier JC, Slovik D, Yismans FJFE, Potts JT, JR (1980) Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial. B Med J 2:1340–1343

    Google Scholar 

  21. Reeve J, Arlot M, Bernat M, Charhon S, Edouard C, Slovik D, Yismans FJFE, Meunier PJ (1981) Calcium-47 kinetics measurements of bone turnover compared to bone histomorphometry in osteoporosis: the influence of human parathyroid fragment (hPTH 1–34) therapy. Metab Bone Dis Rel Res 3:23–30

    Google Scholar 

  22. Reifenstein EC, Albright F, Wells S (1945) The accumulation, interpretation, and presentation of data pertaining to metabolic balances, notably those of calcium, phosphorus and nitrogen. J Clin Endocrinol Metab 5:367–395 and erratum 6:232, 1946

    Google Scholar 

  23. Riggs BL (1983) Treatment of osteoporosis with sodium fluoride: an appraisal. Bone and Mineral Research, Annual 2:366–393

    Google Scholar 

  24. Riggs BL, Hamstra A, DeLuca HF (1981) Assessment of 25-hydroxyvitamin D 1: a hydroxylase reserve in postmenopausal osteoporosis by administration of parathyroid extract. J Clin Endocrinol Metab 53:833–835

    Google Scholar 

  25. Selye H (1933) On the stimulation of new bone formation with parathyroid extract and irradiated ergosterol. Endocrinology 16:547–555

    Google Scholar 

  26. Slovik DM, Neer RM, Potts JT, JR (1981) Short-term effects of synthetic human parathyroid hormone-(1–34) administration on bone mineral metabolismin osteoporotic patients. J Clin Invest 68:1261–1271

    Google Scholar 

  27. Slovik DM, Adams JS, Neer RM, Holick MF, Potts JT, JR (1981) Deficient production of 1,25-dihydroxyvitamin D in elderly osteoporotic patients. N Engl J Med 305:372–374

    Google Scholar 

  28. Steiner AL, Wehrmann RE, Parker CW, Kipnis DM (1973) Radioimmunoassay for measurement of cyclic nucleotides. Adv Cyc Nuc Res 2:51

    Google Scholar 

  29. Wlodarski KH, Reddi AH (1986) Alkaline phosphatase as a marker of osteoinductive cells. Calcif Tissue Int 39:382–385

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The following study quotes the results from the dissertation of J. Heck

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hesch, R.D., Heck, J., Delling, G. et al. Results of a stimulatory therapy of low bone metabolism in osteoporosis with (1–38)hPTH and diphosphonate EHDP. Klin Wochenschr 66, 976–984 (1988). https://doi.org/10.1007/BF01738113

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01738113

Key words

Navigation