1. Goal-directed Treatment for Osteoporosis
Also called “Treat to Target”
Dennis M. Black, PhD
UC San Francisco

2. Current status of Treat-to-Target Thinking
Working group from ASBMR
Initial report Cummings, Lewieki, Cosman, others
Not yet published
Just completed initial report, controversial
Work in progress...setting up conceptual system for future
Imagine it is better yet 2025

3. Purpose of Goals
Anticipate how to use new treatments that have very potent effects on BMD and, perhaps, greater reductions in risk
Improve follow-up of patients on treatment
Improve the approach to selecting initial drug therapy for patients

4. Standard approach to treatment (current)
Start with “1st line” drug, usually a bisphosphonate
Follow up BMD in 1-2 years to see if she is ‘responding’ to the treatment
If ‘responding’, continue
If not responding, consider switching to another anti-resorptive drug or PTH

5. Goal-directed Treatment

6. General principles for drug treatments for osteoporosis
Set a goal for patient
Choose the treatment that has a reasonable chance of reaching that goal
Follow-up periodically –> every 3 – 5 years to reassess the chance of reaching goal

7. 1. Set a goal
If the main reason is a low BMD, then the patient’s goal should be BMD
If the main reason was a high fracture risk, then the goal should be an acceptably low risk
Problematic for several reasons..

8. BMD T-score Goal
If main reason for starting treatment is a T-score ≤ -2.5 at the femoral neck, total hip, or lumbar spine by DXA, then the goal of treatment should be T-score > -2.5 at that site.

9. Why a T-score > -2.5?
Goal should be higher than the level for starting treatment: T-score ≤ -2.5

10. Why a T-score > -2.5?
Goal should be higher than the level for starting treatment: T-score ≤ -2.5
Extension studies show:
When hip T-score remains ≤ -2.5, continuing treatment reduces vertebral fracture risk
When hip T-score becomes > -2.5, little benefit in continuing treatment, so consider a drug holiday1,2
1. Alendronate: Schwartz AV et al. J Bone Miner Res. 2010;25:
2. Zoledronate: Black DM et al. J Bone Miner Res. 2012;27:

11. Initial treatment

12. Choosing Initial Treatment
Treatment should offer at least a 50% chance of achieving the goal within 3 to 5 years.

13. Low Probability of Achieving Goal with Alendronate
Goal FN T-score > -2.5
Currently: T-score = -3.5
Typical gain with alendronate: 4-5% (1/2 t-score)
Probability of reaching the goal: <5% in 3 years
Alendronate
Ms. S
Unpublished data from FIT.

14. Follow-up

15. Follow-up
Patients receiving treatment should be assessed within 3-5 years for achievement of the treatment goal*
* May assess sooner for “response” and adherence

16. Principles of follow up for achievement of goals
Has the patient adhered to treatment?
Aim for at least 80% adherence
If poor adherence persists, consider zoledronate (1/year) or denosumab (2x per year)

17. Principles of follow up for achievement of goals
Has the patient adhered to treatment?
Has the patient had a new fracture or lost BMD?
If a patient has a fracture while on therapy or has had a large decrease in BMD (or is not near “goal”)..Consider switching to a more potent treatment

18. If BMD goal is achieved
If target T-score >-2.5 achieved with a bisphosphonate (Alendronate or Zol)
Stop treatment
Reassess BMD periodically
Restart no more than 5 years later

19. If BMD goal is achieved with non-bisphosphonate therapy
For non-bisphosphonate treatments, like denosumab, teriparatide or SERM, BMD declines rapidly after treatment is stopped.
After achieving the goal, treatment should be continued with an agent that maintains BMD
Best a bisphosphonate

20. BMD goal is not achieved
If T-score is still less than -2.5, what is the probability of achieving the goal with continued therapy?
If <50%, switch to more potent agent
However, switching to denosumab or PTH improves BMD only 1-2% in 12 months
We need more potent treatments

21. Goal directed therapy: Controversies

22. Treat-to-target: Controversies*
No evidence that achievement of BMD goal will reduce risk more than initial course of therapy
We don’t have therapies that increase BMD very much
No evidence about risk changes on therapy by FRAX. People are getting older: risk increasing over time
*McCloskey, Harvey, Kanis. J. Clin Rheum 2015

23. Controversies continued: Many recommendations, little evidence
Need trials comparing anti-fracture efficacy across drugs and combinations
Little data comparing the chance of reaching BMD by starting alternative treatments
Little data about switching treatment
No algorithms for estimating fracture risk for patients taking or switching treatment
An enhanced FRAX?
*McCloskey, Harvey, Kanis. J. Clin Rheum 2015

24. Treat to Target: Summary
Treat to target algorithm is:
Aspirational
A work in progress
We need more evidence about various aspects of this approach including switching treatments
We need more potent treatments

25. Goal-directed work.. Warriors 2015 season start: 23-0
23 Wins, no losses