Short‐term exposure to low‐carbohydrate, high‐fat diets induces low bone mineral density and reduces bone formation in rats

Low‐carbohydrate, high‐fat (LC‐HF) diets are popular for inducing weight loss in adults and are also used as part of a treatment for children with epilepsy. However, potential risks and side effects remain controversial. We investigated effects of LC‐HF diets on growth, bone mineral density (BMD), and turnover in growing rats fed for 4 weeks either normal chow (CH, 9% fat, 33% protein, and 58% carbohydrates), LC‐HF‐1 (66% fat, 33% protein, and 1% carbohydrates), or LC‐HF‐2 (94.5% fat, 4.2% protein, and 1.3% carbohydrates). Rats fed LC‐HF diets accumulated significantly more visceral and bone marrow fat and showed increased leptin but decreased insulin‐like growth‐factor 1 (IGF‐1). Both LC‐HF diets significantly decreased body length (nose to rump), but lengths of humerus, tibia, and femur were significantly reduced with LC‐HF‐2 only. Peripheral quantitative computed tomography (pQCT) and micro‐CT (µCT) independently revealed significant reductions in BMD of tibiae in both LC‐HF groups, and tibial maximum load was impaired. Bone‐formation marker N‐terminal propeptide of type I procollagen was reduced in sera of LC‐HF groups, whereas bone resorption marker CrossLaps remained unchanged. Real‐time PCR analysis revealed significant reductions by 70% to 80% of transcription factors influencing osteoblastogenesis ( Runx2 , osterix , and C/EBPβ ) in bone marrow of rats fed LC‐HF diets. In conclusion, both LC‐HF diets impaired longitudinal growth, BMD, and mechanical properties, possibly mediated by reductions in circulating IGF‐1. Serum bone‐formation markers as well as expression of transcription factors influencing osteoblastogenesis were reduced. This might indicate a lower rate of mesenchymal stem cells differentiating into osteoblasts, thus explaining reduced bone formation with LC‐HF diets. © 2010 American Society for Bone and Mineral Research