In patients with osteoporosis, IGFBP-1 and IGFBP-4 inhibit IGF bone cell proliferation by sequestering IGF-1 and preventing binding to the IGF receptor.(15) IGFBP-3 and IGFBP-5 facilitate IGF action in bone cells; bone matrix proteoglycans do not bind IGFs in the absence of IGFBP-3 and IGFs do not bind to hydroxyapatite in the absence of IGFBP-5.(15) There is also some evidence that IGFBPs regulate bone formation independent of IGF function. This evidence concerns the gene IGFBP5 and osteoporosis.