On rho, a marrow mediator, and estrogen: Their roles in bone strength and "mass" in human females, osteopenias, and osteoporoses—insights from a new paradigm
- Cite this article as:
- Frost, H. J Bone Miner Metab (1998) 16: 113. doi:10.1007/s007740050035
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From existing evidence, this article argues that six assumptions could explain important estrogen effects on a woman's bone strength and "mass". T_h_e_ e_v_i_d_e_n_c_e_: Strains above a "modeling threshold" cause modeling to increase bone strength and "mass"; under lesser strains, modeling stays OFF. Remodeling by basic multicellular units (BMUs) turns bone over in small "packets," and "rho" signifies any difference in how much bone completed BMUs make and resorb. Where strains exceed a lower "remodeling threshold," rho approaches zero, so that remodeling conserves bone. When strains fall below this threshold, as in acute disuse, rho becomes negative, but only next to marrow, so remodeling removes bone only there. The bone lost during menopause also comes from bone next to marrow, so rho became more negative there too. Simultaneously, and in both cases, bone on periosteal and Haversian surfaces is conserved, meaning rho approaches zero there. T_h_e_ a_s_s_u_m_p_t_i_o_n_s_: (A) Estrogen lowers the threshold for BMU creations on all bone surfaces or envelopes, so loss of the hormone at menopause would increase those creations on all envelopes. (B) Estrogen and acute disuse have no direct effect on rho on any bone envelope. (C) Estrogen and acute disuse do affect some mediator(s) in marrow that can secondarily affect BMUs next to it. (D) That mediator has its own strain threshold, and estrogen lowers it. (E) Loss of estrogen raises that threshold, which causes the mediator to make rho more negative in BMUs next to marrow; that would increase bone loss only there, as would acute disuse, because it would reduce strains below that threshold. (F) Estrogen does not affect the modeling threshold, so it would have no direct effect on cortical bone modeling and outside bone diameter (but by affecting bone length, muscle strength, and physical activities, it might affect modeling indirectly). Those assumptions now have considerable support (although it does not yet amount to proof). The text discusses some of their implications for bone and osteoporosis research.