Reduction in bisphosphonate side effect profile using short-term steroid cover

Andrew Biggin; Tina McLean; Mary McQuade; Chris Cowell; Craig Munns

doi:10.1530/boneabs.2.P37

Objectives: Bisphosphonate infusions are associated with numerous adverse effects including acute systemic inflammatory reactions and electrolyte abnormalities. The aims of this study were to evaluate the safety and efficacy of a 3-day course of prednisone on children receiving their first dose of pamidronate or zoledronic acid.

Methods: A retrospective cohort of 166 patients (85 males) were commenced on pamidronate (16%) or zoledronic acid (84%) for treatment of osteoporosis. 58 patients (35%) received a 3-day course of prednisone (1 mg/kg per day) starting on the day of bisphosphonate treatment. All patients received supplementation with calcium (1 g twice-daily) and calcitriol (250 ng twice-daily) for 3 days. Mineral homeostasis was assessed on days 2 and 3. Symptomatology (including fever, nausea, vomiting, headache, and malaise) was evaluated on day 3.

Results: The mean age at commencement of treatment was 11±4 years for both groups (P>0.05). There was a significant decrease in serum calcium and phosphate on day 2 that persisted to day 3 post bisphosphonate infusion for both groups (Table 1). Alkaline phosphatase levels remained unchanged throughout. There were no differences in mineral homeostasis between those receiving prednisone and those who did not. There were no new cases of significant hypocalcemia (<1.9 mmol/l) on day 3 that were not evident by day 2.

Patients receiving steroid cover had a significantly lower incidence of headache, nausea and malaise compared to those who did not (Table 2).

There were no differences in mineral homeostasis or symptomatology between those receiving pamidronate and zoledronic acid.

Table 1 Mineral homeostasis.
	Baseline		Day 2		Day 3
	No steroid	Steroid	No steroid	Steroid	No steroid	Steroid
Ca (mmol/l)	2.35±0.19	2.37±0.13	2.18±0.18*	2.26±0.18*	2.17±0.18*	2.22±0.15*
ALP (U/l)	211±77	232±139	224±73	231±131	206±78	214±128
PO₄ (mmol/l)	1.51±0.22	1.52±0.26	1.18±0.25*	1.06±0.30*	1.00±0.24*	0.90±0.25*
Values represent mean±S.D. *P<0.05 compared to corresponding baseline value.

Table 2 Symptomatology.
	No steroid (n=108 (%))	Steroid (n=58 (%))	Relative risk (95% CI)
Headache	30 (28)	5 (9)	0.3 (0.1–0.8)*
Nausea	36 (33)	7 (12)	0.4 (0.2–0.8)*
Malaise	71 (66)	23 (40)	0.6 (0.4–0.9)*
Vomiting	14 (13)	5 (8)	0.7 (0.3–1.8)
Fever	43 (40)	28 (48)	1.2 (0.9–1.7)
*P<0.05.

Conclusion: A 3-day course of prednisone at the time of initiating intravenous bisphosphonate therapy significantly reduced the incidence of headache, nausea and malaise. Steroid use did not effect bisphosphonate-induced hypocalcemia or hypophosphatemia. Biochemical monitoring for hypocalcemia was not necessary beyond 48 h.

Bone Abstracts

P37