Abstract: Bis-phosphonates such as clodronate, etidronate, pamidronate and alendronate are found to inhibit the degradation of connective tissue matrix protein components in mammals, including humans, and therefore are useful in the therapeutic and prophylactic treatment of mammals against a variety of physiological and pathological connective tissue disorders or extracellular protein degradation disorders including wounds, burns, fractures, lesions, ulcers, cancer and metastasis progression in connective tissues, rheumatoid arthritis and other arthitides, periodontitis, peri-implantitis, cysts, root canal treatment, AIDS, ulceration of the cornea, gastric ulceration, aftae, trauma, acne, psoriasis, loosening of end-osseal hip-protheses.