Lead exposure inhibits fracture healing and is associated with increased chondrogenesis, delay in cartilage mineralization, and a decrease in osteoprogenitor frequency

Environmental Health Perspectives, June, 2005 by Jonathan J. Carmouche, J. Edward Puzas, Xinping Zhang, Prarop Tiyapatanaputi, Deborah A. Cory-Slechta, Robert Gelein, Michael Zuscik, Randy N. Rosier, Brendan F. Boyce, Regis J. O'Keefe, Edward M. Schwarz

The overall clinical significance of Pb inhibition of fracture healing relates to persons with osteoporosis. We have argued that because of the high environmental Pb exposures from the 1940s to 1960s, women currently going through menopause are at an additional risk of osteoporosis (Puzas et al. 2004). It is now well recognized that factors released from bone during resorption, such as TGF-[beta], can act on cells in the bone marrow to induce the production of osteoclastic stimulating factors or to inhibit osteoblastic new bone formation (Evans et al. 1989; Yin et al. 1999). As a consequence of the high bone turnover, which would release Pb from its inactive state in bone hydroxyapatite crystals, an additional imbalance of bone resorption over formation would occur from Pb's preferential toxic effects on osteoblasts. Our results indicate that osteoporotic, Pb-exposed patients may sustain a fragility fracture earlier and heal their fractures at a slower rate compared with non-Pb-exposed osteoporotic individuals. Future investigations into the molecular mechanisms of Pb effects on osteoporosis and fracture healing are warranted.

Table 1. In vivo Pb bone exposures.

Pb in drinking water (ppm)   [micro]g/Pb/g dry bone

0                             0.08 [  or -] 0.01
55                            33.3 [  or -] 2.80
230                           117.3 [  or -] 11.13
2,300                         472.88 [  or -] 61.98
5,800                         682.41 [  or -] 142.75

n = 4/treatment group. Data presented are mean [  or -]SD.

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