Method of correcting imbalance between bone resorption and bone formation and kits and compositions therefor
View Patent ↗Compounds, methods, uses, compositions, kits and packages for the treatment of imbalance between bone resorption and bone formation, based on uses of 4-phenyl-2 propionamidotetralin (4-P-PDOT) and analogs, derivatives, prodrugs, precursors thereof, and salts thereof, are described.
1. A method comprising: (a) identifying a subject suffering from imbalance between bone resorption and bone formation; and (b) administering to said subject a therapeutically effective amount of (i) 4-phenyl-2-propionamidotetralin (4-P-PDOT); (ii) a conjugate of 4-P-PDOT; (iii) a pharmaceutical acceptable salt of (i) or (ii); or (iv) any combination of (i) to (iii), whereby imbalance between bone resorption and bone formation is improved in said subject.
2. The method of claim 1 , wherein the subject suffers from osteoporosis.
3. The method of claim 1 , wherein the subject suffers from Paget disease.
4. The method of claim 1 , wherein the subject suffers from osteolytic bone cancer.
5. The method of claim 1 , wherein the subject suffers from arthritis characterised by the presence of an inflammatory cytokine that induces osteoclasts.
6. The method of claim 1 , wherein said administration is a single bolus administration.
7. The method of claim 1 , wherein said administration is a daily administration.
8. The method of claim 1 , wherein said therapeutically effective amount is between 0.001 and 500 mg/kg of subject/day.
9. The method of claim 1 , wherein said improvement of imbalance between bone resorption and bone formation comprises at least one of: an inhibition of bone resorption; an inhibition of osteoclast differentiation; an increase in bone mineral density (BMD); an increase in bone mineral content (BMC); an increase of density of pure cortical bone; an increase of mean density of total bone; an increase of cortical thickness; an increase of pure cortical area assigned to be cortical; an increase of tibial diaphyseal total bone areas; an increase of mineralization apposition rate; an increase of bone formation rate/bone surface referent; an increase of mineralizing surface for endocortical or periosteal surface; a decrease of serum alkaline phosphatase; a decrease of intra-cortical regions of hypo-mineralized osteoid; a decrease of osteoid thickness and a decrease of osteoid condensation.
10. The method of claim 1 , wherein said correction of imbalance between bone resorption and bone formation comprises an inhibition of bone resorption.
11. The method of claim 1 , wherein said correction of imbalance between bone resorption and bone formation comprises an inhibition of osteoclast differentiation.
12. The method of claim 1 , wherein said correction of imbalance between bone resorption and bone formation comprises an increase in bone mineral density (BMD).
13. The method of claim 1 , wherein said correction of imbalance between bone resorption and bone formation comprises an increase in bone mineral content (BMC).
14. The method of claim 1 , which further comprises the administration of another agent selected from the group consisting of a bisphosphonate, raloxifene, nasal calcitonin and teriparatide.
15. The method of claim 1 , wherein the subject is a human.