Declining estrogen production after menopause causes osteoporosis in which the resorption of bone exceeds the increase in bone formation. We recently found that mice deficient in the β-subunit of follicle-stimulating hormone (FSHβ) are protected from bone loss despite severe estrogen deficiency. Here we show that FSHβ-deficient mice have lowered TNFα levels. However, TNFα-deficient mice are resistant to hypogonadal bone loss despite having elevated FSH, suggesting that TNFα is critical to the effect of FSH on bone mass. We find that FSH directly stimulates TNFα production from bone marrow granulocytes and macrophages. We also explore how TNFα up-regulation induces bone loss. By modeling the known actions of TNFα, we attribute the high-turnover bone loss to an expanded osteoclast precursor pool, together with enhanced osteoblast formation. TNFα inhibits osteoblastogenesis in the presence of ascorbic acid in culture medium, but in its absence this effect becomes stimulatory; thus, ascorbic acid reverses the true action of TNFα. Likewise, ascorbic acid blunts the effects of TNFα in stimulating osteoclast formation. We propose that hypogonadal bone loss is caused, at least in part, by enhanced FSH secretion, which in turn increases TNFα production to expand the number of bone marrow osteoclast precursors. Ascorbic acid may prevent FSH-induced hypogonadal bone loss by modulating the catabolic actions of TNFα.