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Modulation of PTH‐stimulated osteoclastic resorption by bisphosphonates in fetal mouse bone explants
Author(s) -
van der Pluijm Gabri,
Löwik Clemens W.G.M.,
de Groot Henny,
Alblas Marcel J.,
van der WeePals Lianne J. A.,
Bijvoet OLAV L. M.,
Papapoulos Socrates E.
Publication year - 1991
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650061110
Subject(s) - bone resorption , resorption , osteoclast , medicine , endocrinology , fetus , chemistry , parathyroid hormone , bone remodeling , calcium , biology , pregnancy , receptor , genetics
We examined the effects of the bisphosphonates Cl 2 MDP, APD, and Me 2 APD on osteoclastic resorption in the absence and presence of PTH using fetal mouse osteoclast‐free bone explants cocultured with fetal liver as a source of osteoclast precursors. Results revealed qualitative and quantitative differencs among the bisphosphonates tested. With Cl 2 MDP and APD fractional inhibition of resorption (measured as 45 Ca release) in the presence of PTH was proportional to that obtained in its absence. In contrast, Me 2 APD, which is the most potent inhibitor of the three, was found at low concentrations (≤5 × 10 −7 M) to enhance the PTH‐stimulated osteoclastic resorption. APD as well, at concentrations that could not inhibit resorption, had a similar effect, but Cl 2 MDP did not. These studies describe a new phenomenon, that low doses of nitrogen‐containing bisphosphonates can act synergistically with PTH and enhance osteoclastic resorption. These findings may have clinical implications in the management of patients with increased osteoclastic resorption due to parathyroid overactivity.