This study identifies Malat1, a long noncoding RNA (lncRNA), as a protective factor against osteoporosis and bone metastasis. Malat1 is downregulated during osteoclastogenesis in both humans and mice. Genetic deletion of Malat1 in mice leads to osteoporosis and increased bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic restoration of Malat1. Mechanistically, Malat1 binds to Tead3, a macrophage-osteoclast-specific protein, blocking its interaction with and activation of Nfatc1, a master regulator of osteoclastogenesis. Single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. These findings identify Malat1 as an lncRNA that protects against osteoporosis and bone metastasis by inhibiting osteoclast differentiation.This study identifies Malat1, a long noncoding RNA (lncRNA), as a protective factor against osteoporosis and bone metastasis. Malat1 is downregulated during osteoclastogenesis in both humans and mice. Genetic deletion of Malat1 in mice leads to osteoporosis and increased bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic restoration of Malat1. Mechanistically, Malat1 binds to Tead3, a macrophage-osteoclast-specific protein, blocking its interaction with and activation of Nfatc1, a master regulator of osteoclastogenesis. Single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. These findings identify Malat1 as an lncRNA that protects against osteoporosis and bone metastasis by inhibiting osteoclast differentiation.