Analogues of bovine and human parathyroid hormone, wherein twenty-fifth, twenty-six and twenty-seventh positions of the natural hormone, Arg-Lys-Lys- each have been substituted with Ala, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val have been found to retain bone cell effect with minimal effects on blood pressure and smooth muscle, including cardiac muscle. It has further been found that this effect can be obtained by using a synthetic PTH containing only the first 34 amino acids of PTH, with substitution at the twenty-fifth, twenty-sixth and twenty-seventh amino acids as described. These analogues of PTH also are effective in the treatment of osteoporosis and other bone diseases.

A method of treating osteoporosis is disclosed by administering orally a single daily dosage of phosphate in the evening in an amount, e.g., about 10 mg/kg body weight or less which is effective to raise serum parathyroid hormone levels of the subject being treated.

Systemic delivery of parathyroid hormone to a mammalian host is accomplished by inhalation through the mouth of a dispersion of an N-terminal fragment of PTH. It has been found that such respiratory delivery of the PTH fragment provides a pulsatile concentration profile of the PTH in the host's serum. PTH fragment compositions include dry powder formulations having the PTH present in a dry bulking powder, liquid solutions or suspensions suitable for nebulization, and aerosol propellants suitable for use in a metered dose inhaler.

The present invention provides methods of increasing bone mass in a human or other animal subject afflicted with osteoporosis, comprising a thirty(30)-day treatment period, comprised of a parathyroid hormone administration regimen and a bisphosphonate administration regimen, wherein (a) said parathyroid hormone administration regimen comprises the administration to said subject of parathyroid hormone at one or more level of from about 4 IU/kg per day to about 15 IU/kg per day that said parathyroid hormone is administered, provided that said parathyroid hormone is administered at least one day every seven days of every said thirty(30)-day treatment periods; and wherein (b) said bisphosphonate administration regimen comprises the administration to said subject of a bisphosphonate at a level of from about 0.0005 mgP/kg to about 1.0 mgP/kg per day that said bisphosphonate is administered, provided that said bisphosphonate is administered at least 1 day of every said thirty(30)-day treatment period.

A stabilized pharmaceutical composition in the form of a solution for parenteral administration of a parathyroid hormone is described wherein the therapeutically active ingredient is stabilized with a buffer and a polyol. Preferred preparations contain in an aqueous solution human PTH(1-34), mannitol, an acetate or tartrate buffering agent and m-cresol or benzyl alcohol as a preservative.