Osteoporosis Rx Update: Sequential and Combination Therapy

Article

New study results shed light on questions about the effect of combining drugs to treat osteoporosis and what happens after a switch from one drug to another.

Hofbauer LC, Rachner TD. [Comment] More DATA to guide sequential osteoporosis therapy. Lancet. Online: 02 July 2015. DOI: 10.1016/S0140-6736(15)61175-8.

Leder BJ, Tsai JN, Uihlein AV, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.Lancet. Online: 02 July 2015. DOI: 10.1016/S0140-6736(15)61120-5. 

 

When postmenopausal osteoporotoic women were switched from 24 months of teriparatide to 24 months of denosumab, bone mineral density (BMD) continued to increase.

When they were switched from 24 months of the combination of teriparatide and denosumab to 24 months of denosumabalone, BMDcontinued to increase, at a slower rate.

But when they were switched from 24 months of denosumab to 24 months of teriparatide, BMD decreased for several months, before it started to recover.

The DATA-Switch study is an extension of the DATA trial, a randomized, controlled trial of denosumab, teriparatide, and the combination.

The original 12-month DATA trial of 100 women found that for example teriparatide increased BMD at the spine by 6.2%. Denosumab increased BMD by 5.5%. The combination increased BMD by 9.1%. The 24-month trial found that teriparatide increased BMD by 9.5%, denosumab by 8.3%, and the combination by 12.9%.

 

Increase in BMD from 0 to 12 Months

 

Teriparatide

Denosumab

Combination

Lumbar spine

6.2%

5.5%

9.1%

Femoral neck

0.8%

2.1%

4.2%

Total hip

0.7%

2.5%

4.9%

Distal radius

-1.8%

1.7%

2.6%

Increase in BMD from 0 to 24 Months

 

Teriparatide

Denosumab

Combination

Lumbar spine

9.5%

8.3%

12.9%

Femoral neck

2.8%

4.1%

6.8%

Total hip

2.0%

3.2%

6.3%

Distal radius

-1.7%

2.1%

2.2%

The DATA-Switch study was designed to answer several unanswered questions relevant to real-world treatment of osteoporosis – combination treatment, switching drugs, and long-term outcomes.

The remaining 69 patients were switched from one regimen to the other, as they would be in clinical practice when they reach the recommended time limits of osteoporosis drugs. Patients who were switched to denosumab did better than patients who were switched to teriparatide. First, the overall results of 48 months of treatment:

Change in BMD from 0 to 48 Months (69 women)

 

Teriparatide to denosumab

Denosumab to teriparatide

Combination to denosumab

Lumbar spine

18.3%

14.0%

16.0%

Femoral neck

8.3%

*4.9%

9.1%

Total hip

6.6%

*2.8%

8.6%

Distal radius

0.0%

*-1.8%

2.8%

* Statistically significant

Second, the results of the last 24 months of the crossover treatment:

Change in BMD from 24 to 48 Months

 

Teriparatide to denosumab

Denosumab to teriparatide

Combination to denosumab

Lumbar spine

8.6%

4.8%

3.4%

Femoral neck

*5.6%

*1.2%

2.1%

Total hip

*4.7%

*-0.7%

*2.2%

Distal radius

*2.3%

*-5.0%

*0.5%

* Statistically significant

When women were switched from denosumab to teriparatide, BMD decreased for 6 or more months, until it started to recover, and reached the values in the tables above. However, the distal radius BMD never recovered, and the total hip BMD was only beginning to recover by the end of the trial (Leder, Figure 3 and Table 2).

The editorial writers made three recommendations:

-- For sequential monotherapy, teriparatide followed by denosumab gives a sustained increase of BMD;

-- Combination therapy with teriparatide and denosumab gives the greatest gain in BMD when followed by denosumab;

-- Denosumab followed by teriparatide monotherapy should be avoided because it results in a transient loss of BMD at the spine and the hip, and progressive loss of BMD at the distal radius.

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