Combination therapy with controlled-release CNP agonists

A method of stimulating bone growth in a patient, the method comprising administering to the patient an effective amount of a controlled-release C-type natriuretic peptide (CNP) agonist, wherein the patient is also administered human growth hormone resulting in a synergistic increase in bone growth from the controlled-release CNP agonist and the human growth hormone acting in combination;

• wherein the controlled-release CNP agonist releases a CNP moiety, the amino acid sequence of which consists of SEQ ID NO:24, under physiological conditions with a release half-life of at least 6 hours, wherein the controlled-release CNP agonist is a compound of formula (IIf):
• or a pharmaceutically acceptable salt thereof;
• wherein
• the unmarked dashed line indicates the attachment to a nitrogen provided by the side-chain of the lysine at position 26 of the CNP moiety by forming an amide bond;
• and
• the dashed line marked with the asterisk indicates attachment to —Z having the structure
• wherein
• each —Za is
• wherein
• each c1 is an integer independently ranging from 200 to 250.