Osteocyte density and viability in postmenopausal women after long-term bisphosphonate therapy
Qiu S, Divine G, Honasoge M, Bhan A, Levy S, Warner E, Rao SD. Osteocyte density and viability in postmenopausal women after long-term bisphosphonate therapy. Journal of Bone and Mineral Research 2018; 33(Supplement 1).
Journal of Bone and Mineral Research
Our previous study indicated that short-term (1 year) bisphosphonate (BP) treatment did not affect osteocyte viability in postmenopausal women, but the effect of long-term BP treatment on osteocytes remains unclear.Iliac bone biopsies were obtained from 80 age matched white postmenopausal women (43 normal volunteers and 37 BP treated patients). The duration of BP exposure was 2-17y (median: 7y). Five μm Goldner & trichorome stained sections were used to measure trabecular bone osteocyte density [Ot.Dn (/mm2)], empty lacunar density [EL.Dn (/mm2)], total lacunar density [(TL.Dn (/mm2)], and percent empty lacunae [EL.Dn/TL.Dn (%)]. The difference in each osteocyte-related variable was compared between the 2 groups.As shown in the Table, Ot.Dn was significantly lower in patients with BP treatment than in normal women. In contrast, EL.Dn in BP treated patients was >3 times higher than in the normal women. The extremely increased EL.Dn in BP treated patients resulted in a 4 times higher EL.Dn/TL.Dn ratio. There was also a significant 14% reduction in TL.Dn in the BP treated group. There was no significant correlation between the duration of BP exposure and any osteocyte-related variable.In conclusion, we found that osteocyte viability is dramatically reduced after long-term BP treatment. The significant decrease in total lacunar density and a very high empty lacunar density suggest that part of empty lacunae resulting from osteocyte death are obliterated by mineralized tissue. Combined with our previous work, we postulate that the loss of osteocytes after long-term BP treatment is not due to BP toxicity but rather caused by prolonged and sustained inhibition of bone remodeling. Accumulation of unremodeled old bone characterized by low osteocyte density and hypermineralization will increase bone fragility.