Paget disease is a disorder of bone of unknown etiology with increased bone turnover that results in defective bone microarchitecture. Defective microarchitecture results in deformity in skull and long bones, arthritis, deafness and pathologic fractures. Therefore, quality of life in patients with Paget disease is worse than normal population [1].

While formerly calcitonin was used in treatment of symptomatic Paget disease, bisphosphonates are used currently for the same indication. In clinical use, zoledronic acid provided a better clinical response with 96% normalization in ALP level with one dose, whereas 89% normalization was obtained after six months of treatment with other bisphosphonates. A significant improvement in quality of life was reported with zoledronic acid treatment [2]. Normalization in bone turnover, restoration in structure of bone, and regression in bone lesions were observed with bisphosphonate treatment [3]. Remission was shorter with other bisphosphonates and retreatment was required in every 1-3 years [4]. Zoledronic acid shows high affinity to bone [5]. Quite low recurrence rates were reported in patients with Paget disease treated with zoledronic acid [6].

We retrospectively reviewed relapse and remission rates with single dose zoledronic acid in patients with Paget disease.

Alkaline Phosphates (ALP), Osteocalcin (OC), and Deoxypyridinoline (DPD) levels measured before and at 6^th, 12^th, 18^th months of treatment were retrospectively reviewed in twelve patients diagnosed with Paget disease (having typical symptoms, high ALP, OC, and DPD levels, bone lesions relevant with Paget disease on direct radiographs or bone scintigraphy) treated with zoledronic acid between October 2011 and October 2013. Vitamin D (400-1000 IU/ day) and calcium (1 gr/day) supplementations were given to all patients before and after treatment with zoledronic acid. Neither hypocalcemia nor hypocalcemic symptoms were observed during zoledronic acid treatment. Subfebrile fever and myalgias were observed in three patients and were controlled with paracetamol.

Patients whose ALP levels reduced by 75% of the basal levels or within normal range according to the reference values were regarded as remission and 20% increase in the basal levels was regarded as relapse.

Total serum ALP was measured with Roche Hitachi 797 and normal reference range was 40–129 U/L. Serum OC and urine DPD were measured with Immulife 1000 and normal reference range was; 2–15 ng/ml, and 2.3–5.4 mmol/L, respectively.

Statistical analysis

Statistical analysis was conducted by using SPSS version 16. Student t test was used in comparison between two groups. A p value<0.05 was regarded as statistically significant

Records of twelve patients with Paget disease were retrospectively analysed. Mean age of the patients was 58.37 ± 10. 92 and there were 9 males and 3 females. Nine of these 12 patients were newly diagnosed and received no therapy before the study. Remaining three patients were previously diagnosed patients in whom remission could not be provided with risedronate (2 patients) or pamidronate (1 patient).

Figure 1:Remission after treatment.

Table 1: Pretreatment and posttreatment results.

Pretreatment results were: ALP: 473 ± 256 U/L; DPD: 14.99 ± 7.63 mmol/L; OC: 21.09 ± 3.18 ng/ml. The results at the 6^th month of therapy were: ALP: 82 ± 13 U/L; DPD: 5.14 ± 1.11 mmol/L; OC: 8.57 ± 4.31 ng/ml. Remission was provided in all patients (Table 1). Comparison of the results of 12^th and 18^th months revealed that remission was persistent (Figure 1). There was statistically significant difference between pretreatment values and values at 6^th, 12^th and 18^th months of treatment (p<0.05). No statistically significant difference between the levels measured at 6^th, 12^th and 18^th months of treatment was detected (p>0.05).

In a study by Ried et al. [2], single dose of zoledronic acid (5 mg) was given to 176 patiets and 60 days of treament with risedronate (30mg/day) was given to 171 patients. Remission was provided at the 6^th month of treatment in 74.3% of patients treated with risedronate and 96% of patients treated with zoledronic acid [2]. In a study by Merlotti et al. [7], pamidronate was given to 60 patients at a dose of 30 mg/day in sequential two days/per three months and single dose of 4 mg zoledronic acid was given to 30 patients. Remission rate was 45% in the pamidronate group and 97% in the zoledronic acid group at the 6^th month of treatment [7]. In our study, remission was obtained in all patients with a single dose of 5 mg zoledronic acid at the 6^th month of treatment. Two of these patients treated with risedronate and one treated with pamidronate previously did not have remission. All of these three patients remitted with a single dose of zoledronic acid.

In a study by Ried et al. [8], zoledronic acid was given to 152 patients; risedronate to 112 patients and followed-up for a period of 6.5 years. Relapse rate was 20% in risedronate group and 0.7% (1/152) in zoledronic acid group. No relapse was observed in our study in the follow-up duration of 18 months.

This study showed that, remission can be achieved in all 12 patients at the 6^th month and can be maintained at the 18^th month of zoledronic acid treatment. No relapse was observed during the study period.

Limitations of the study; Case series observations. Only the results of patients treated with zoledronic acid were evaluated. Comparison with other bisphosphonates cannot be made. Long term results cannot be given as the follow-up duration was short.

In conclusion zoledronic acid can be recommended a good therapeutic option treatment of Paget disease.