Abaloparatide and Denosumab Combination for Bone Mineral Density
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Solution Overview
Problem
Current treatments for osteoporosis, such as denosumab, often result in high risk of fractures due to bone loss and adverse events, with limited options for patients who experience declining bone mineral density or fractures despite treatment, and switching to teriparatide can lead to substantial BMD loss.
Innovation Solution
Combining abaloparatide, a PTHrP(1-34) analogue, with denosumab to administer concomitantly or sequentially, providing a therapeutically effective amount to enhance bone mineral density and reduce adverse events, particularly in patients at high risk for fractures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-generated harmful factors
If denosumab is used to treat osteoporosis, then bone resorption is inhibited, but bone mineral density declines and fracture risk increases
Solution Approach 1:
The patent combines denosumab (an antiresorptive agent) with abaloparatide (an anabolic agent) into a single composition for simultaneous administration. This merging allows the therapy to both inhibit bone resorption and stimulate bone formation, thereby increasing bone mineral density and reducing fracture risk while maintaining the benefits of denosumab monotherapy.
2Reliability
If teriparatide is used to increase bone mineral density, then bone formation is stimulated, but substantial BMD loss occurs in patients switching from denosumab
Solution Approach 1:
The patent merges the antiresorptive effects of denosumab with the anabolic effects of abaloparatide in a single composition. This combination prevents the substantial BMD loss observed when switching from denosumab to teriparatide by maintaining continuous suppression of bone resorption while stimulating bone formation, thereby preserving and increasing bone mineral density.
3Reliability
If abaloparatide is administered to stimulate bone formation, then bone mineral density increases, but bone resorption may be increased
Solution Approach 1:
The patent combines abaloparatide with denosumab in a single composition, allowing the denosumab component to suppress bone resorption while the abaloparatide component stimulates bone formation. This merging resolves the contradiction by simultaneously achieving increased bone mineral density through anabolic effects while preventing increased bone resorption through antiresorptive effects.
4Reliability
If combination therapy with abaloparatide and denosumab is used, then bone mineral density increases and adverse events are reduced, but treatment complexity increases
Solution Approach 1:
The patent merges two separate medications (abaloparatide and denosumab) into a single fixed-dose combination composition. This merging simplifies treatment by eliminating the need for separate administrations, reducing pill burden, and streamlining the treatment regimen while maintaining the therapeutic benefits of both agents for increasing bone mineral density and reducing adverse events.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination therapy significantly increases bone mineral density in the spine and hip, reduces adverse events, and promotes bone formation without increasing bone resorption, offering a more effective treatment for osteoporosis and fracture healing.
Implementation Method 1
PTHrP, especially the C-terminal 1-36 secretory product and certain analogs, are known to be useful for the treatment of osteoporosis and related disorders by stimulating bone formation to improve bone mineral density (BMD)
Implementation Method 2
Some patients on denosumab treatment for osteoporosis remain at high risk for fracture
Data Source
AI summary
Provided herein are methods for increasing bone mineral density, treating osteoporosis and the like, that include administration of abaloparatide in combination with denosumab.