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J Endocrinol Invest. 2011 Dec;34(11):e392-7. doi: 10.3275/7864. Epub 2011 Jul 12.

Prevention of chemotherapy-induced osteoporosis by cyclophosphamide with a long-acting form of parathyroid hormone.

Author information

1
Department of Pediatric Endocrinology, Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, NY, USA. tponnapa@montefiore.org

Abstract

BACKGROUND:

Most chemotherapeutics reduce bone mineral density (BMD) and increase risk for fractures by causing gonadal suppression, which in turn increases bone removal. Cyclophosphamide (CYP) also has a direct effect of inhibiting bone formation and removal, making the resulting bone loss particularly difficult to treat with antiresorptive therapy.

AIM:

We tested whether a single dose of the anabolic agent PTH linked to a collagen binding domain (PTHCBD) could prevent the effects of CYP-induced bone loss.

METHODS:

Mice received either buffer alone, CYP, or CYP+ PTH-CBD. BMD and alkaline phosphatase were measured every 2 weeks for a total of 8 weeks.

RESULTS:

After 6 weeks, mice treated with CYP showed expected reductions in BMD (increase from baseline: 7.4 ± 6.9 vs 24.35 ± 4.86% in mice without chemotherapy, p<0.05) and decrease in alkaline phosphatase levels (42.78 ± 6.06 vs 60.62 ± 6.23 IU/l in mice without chemotherapy, p<0.05), consistent with osteoporosis from impaired bone formation. Administration of a single dose of PTH-CBD (320 μg/kg ip) prior to CYP treatment improved BMD (change from baseline: 23.4 ± 5.4 vs 7.4 ± 6.9%, CYP treatment alone, p<0.05) and increased alkaline phosphatase levels (50.14 ± 4.86 vs 42.78 ± 6.06 IU/l in CYP treatment alone, p<0.05). BMD values and alkaline phosphatase levels were restored to those seen in mice not receiving chemotherapy.

CONCLUSIONS:

A single dose of PTHCBD prior to chemotherapy reversed CYP-induced suppression of bone formation and prevented CYP-induced bone loss in mice.

PMID:
21750397
DOI:
10.3275/7864
[Indexed for MEDLINE]

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