Preliminary results for a ramping model of pamidronate administration

Alyssa K Givens; Steven Bachrach; H Theodore Harcke; Heidi H Kecskemethy

doi:10.1530/boneabs.6.P136

Objectives: Examine the effects of a ramped dosage schedule of pamidronate on BMD, fracture rate and location compared to a uniform 5-course regimen. The ramping regimen is intended to alter the tendency for post-treatment fractures to occur at the juncture of pamidronate bands where stress-riser related fractures have been described.

Methods: Ten non-ambulatory children (seven females) with neuromuscular disabilities who received IV pamidronate with a tapering dose were identified (Group 1) and compared to a cohort of 25 patients who received a uniform 5-course regimen (Group 2).

Periodic DXA evaluations were performed every 6 months. Fracture rate before and after treatment was calculated using the person-years method, with post-treatment observation starting with the first dose. Radiographs were examined for location of fracture.

Results: Over treatment, lumbar spine (LS) BMD increased 47.7% and lateral distal femur (LDF) BMD of all regions (R1, R2 & R3) increased 38.0%, 30.1%, and 22.9%, respectively. Group 2 BMD increases were 40.3% at LS and 68.3%, 15.6% and 10.8%, for LDF R1–R3. Mean post-treatment observation period was 4.6 years. Two of ten children in Group 1 sustained a fracture during treatment (right distal femur at 3 weeks, left foot at 10.5 months) but no fractures occurred after treatment ended. Pre and post-treatment fracture rates were 18.5% and 4.3%. Four of 25 in Group 2 sustained 5 fractures after treatment over the same time period; 80% occurred at pamidronate bands. Pre and post-treatment fracture rates in were 36% and 13% for Group 2.


Schedule	Dose	Number of courses*	Total drug
Ramped dose (Group 1)	0.5 mg/kg per day×3 days	1	18.5 mg/kg over 24 months
	1 mg/kg per day×3 days	4
	1 mg/kg per day×2 days	2
	1 mg/kg per day×1 day	1
Uniform dose (Group 2)	1 mg/kg per day×3 days	5	15 mg/kg over 13.6 months
*3–4 months between courses.

Conclusion: Regardless of dosing schedule, BMD improved, post-treatment fracture rate decreased after treatment started, and fractures occurred during treatment. After treatment ended, no fractures occurred in those who received the ramped dosage, suggesting reduction in stress riser formation. A longer treatment period and greater total amount of drug administered with the ramped dose might be contributory. Further study of a ramped dosing schedule is warranted.

Disclosure: The authors declared no competing interests.

Bone Abstracts

P136