Chronic exposure to fluoride is a public health problem worldwide. We explored the relationship between fluoride exposure, orthopedic injuries and bone formation markers alkaline phosphatase (ALP), bone Gla protein (BGP) in participants with coal-burning fluorosis in Hehua Village (coal-burning fluorosis endemic area) in Zhijin County of Guizhou Province and Zhangguan Village (non-fluoride contaminated area) in Anshun City of Guizhou Province. Environmental samples were collected and fluoride contents were examined using a fluoride ion-selective electrode. Dental fluorosis and skeletal fluorosis of 295 participants from Hehua Village and 85 participants from Zhangguan Village were diagnosed with informed consent. Urinary samples and peripheral blood samples were collected from the participants to determine urinary fluoride (UF), ALP activity, and BGP content. The results showed that fluoride contents in rice, pepper, corn, drinking water, clay, vegetable-grown soil, coal and indoor and outdoor air were significantly higher than those in the control area, but lower than the previously reported values. With the increases of UF concentration, the ALP activity and BGP content significantly increased, the severity of skeletal fluorosis was greater, but with no significant changes in dental fluorosis. There was positive correlation between the severity of skeletal fluorosis and ALP activity, BGP content. These results indicated that low fluoride exposure could cause orthopedic injuries. ALP and BGP could be used to evaluate the bone turnover in patients with skeletal fluorosis, which would be useful in the auxiliary diagnosis and therapeutic evaluation of skeletal fluorosis.