Lead exposure inhibits fracture healing and is associated with increased chondrogenesis, delay in cartilage mineralization, and a decrease in osteoprogenitor frequency.
Lead exposure continues to be a significant public health problem. In addition to acute toxicity, Pb has an extremely long half-life in bone. Individuals with past exposure develop increased blood Pb levels during periods of high bone turnover or resorption. Pb is known to affect osteoblasts, osteoclasts, and chondrocytes and has been associated with osteoporosis. However, its effects on skeletal repair have not been studied. We exposed C57/B6 mice to various concentrations of Pb acetate in their drinking water to achieve environmentally relevant blood Pb levels, measured by atomic absorption. After exposure for 6 weeks, each mouse underwent closed tibia fracture. Radiographs were followed and histologic analysis was performed at 7, 14, and 21 days. In mice exposed to low Pb concentrations, fracture healing was characterized by a delay in bridging cartilage formation, decreased collagen type II and type X expression at 7 days, a 5-fold increase in cartilage formation at day 14 associated with delayed maturation and calcification, and a persistence of cartilage at day 21. Fibrous nonunions at 21 days were prevalent in mice receiving very high Pb exposures. Pb significantly inhibited ex vivo bone nodule formation but had no effect on osteoclasts isolated from Pb-exposed animals. No significant effects on osteoclast number or activity were observed. We conclude that Pb delays fracture healing at environmentally relevant doses and induces fibrous nonunions at higher doses by inhibiting the progression of endochondral ossification.
Carmouche
Jonathan J
JJ
Center for Musculoskeletal Research, University of Rochester Medical Center , University of Rochester, School of Medicine and Dentistry, Rochester, New York 14642, USA.
Puzas
J Edward
JE
Zhang
Xinping
X
Tiyapatanaputi
Prarop
P
Cory-Slechta
Deborah A
DA
Gelein
Robert
R
Zuscik
Michael
M
Rosier
Randy N
RN
Boyce
Brendan F
BF
O'Keefe
Regis J
RJ
Schwarz
Edward M
EM
D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D007854:Lead / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D013977:Tibia / Q000187:drug effects / Q000293:injuries
D007854:Lead