Abstract: The present invention relates to a method of treating metabolic bone diseases in a patient, which comprises the modulation of PEX activity to modulate the bone micro-environmental concentrations of critical bone anabolic agents, namely PTH and PTHrP. The present invention also provides the use Of inhibitors of PEX activity, such as, the use of inhibitors of NEP and/or ECE and/or PEX such as phosphoramidon, and analogs thereof, to modulate and preferably increase PTH/PTHrP levels in bone microenvironment to consequently result in an increase in bone formation, as confirmed by serum bone markers, namely, osteocalcin, to thereby provide a novel method for treating metabolic bone diseases, such as osteomalacia, osteoporosis, osteopetrosis, Paget's disease and X-linked hypophosphatemic rickets.

Abstract: The invention provides method of diagnosing bone disease and/or a susceptibility thereto, in an individual. The method includes screening a biological sample obtained from the individual for one or more genetic indicators of bone disease in said PTHrP gene of the individual, and diagnosing the individual based on a characterization of the genetic indictor(s) detected. A genetic indicator of the invention preferably includes a genetic segment of a PTHrP gene. More preferably, a genetic segment of a PTHrP gene includes a VNTR containing region. The invention further relates to a transgenic non-human mammal for the study of bone disease and/or bone conditions, the mammal having a disruption or inactivation of a PTHrP gene or portion thereof specifically in osteoblast cells.