Long Term Outcome of Bisphosphonate Therapy in Patients with Primary Hyperparathyroidism

Abstract

Context: Primary hyperparathyroidism (PHPT) is commonly associated with reduced bone mineral density (BMD) presenting with osteoporosis, increasing the risk of bone fragility fractures in these patients. Bisphosphonates, due to their anti-resorptive action, are known to improve the BMD and reduce the risk of bone fragility fractures. Therefore, bisphosphonates are considered as an alternative to surgical treatment in managing osteoporosis in PHPT patients. Aim: The aim of this observational study was to assess the effect of long term bisphosphonate therapy on BMD, bone fragility fracture and biochemical markers of bone metabolism in patients with PHPT. Methodology: Fifty patients (mean age 74 years) with PHPT who were treated with long term bisphosphonate therapy were studied retrospectively. The mean baseline (before commencing bisphosphonate therapy) BMD T-scores for lumbar spine (L2-L4) and left femoral neck were −2.5 and −2.1, respectively. Fourteen patients had bone fragility fractures before initiation of bisphosphonate therapy. Results: After an average of 5 years of bisphosphonate treatment, there was a significant increase in lumbar BMD T-score (−2.5 to −2.1, p = 0.013) and a non-significant change in left femoral neck BMD T-score (−2.1 to −2.2, p = 0.497). There was no increase in bone fragility fracture rate (p = 0.167). Serum corrected calcium reduced from 2.74 mmol/L to 2.60 mmol/L (p < 0.001) and urine calcium to creatinine ratio from 0.70 to 0.55 (p < 0.0001), both within the reference range. Conclusions: Our study suggests that long term bisphosphonate therapy improves lumbar BMD and prevents increase in bone fragility fracture rate. Additionally it improves hypercalcaemia in PHPT.

Contemporary Medical Management of Primary Hyperparathyroidism: A Systematic Review

“…Only two out of the three ( 45 , 47 ) reports on s-calcium which is unchanged in one and decreases in the other during treatment, PTH, CTX, and alkaline phosphatase are reported to decline. Vera et al ( 47 ) reports a small and insignificant decline in BMD, whereas Yeh et al and Segula et al ( 45 , 48 ) in accordance with most other studies report an increase at spine and hip. The prior study also reports a markedly increased risk of fractures compared to patients treated surgically (PTX) as well as controls, but the bisphosphonate subgroup also did have a much lower BMD at baseline compared to the other two groups.…”

“…The articles concerning etidronate (2) ( 40 , 41 ), risedronate (2) ( 42 , 43 ), neridronate (1) ( 44 ), and mixed bisphosphonates (4) ( 45 – 48 ) were, due to the limited number of studies, pooled into one group called mixed bisphosphonates (see Table S4 in Supplementary Material). The articles reporting on effects of etidronate, risedronate, and neridronate used one drug only for all included subjects, whereas the articles on mixed bisphosphonates used a variety of different bisphosphonates within the individual study.…”

“…The articles reporting on effects of etidronate, risedronate, and neridronate used one drug only for all included subjects, whereas the articles on mixed bisphosphonates used a variety of different bisphosphonates within the individual study. One article on etidronate ( 40 ), one on risedronate ( 42 ), and three reporting on mixed bisphosphonates ( 45 – 47 ) provided data to the calculation of an average decrease in s-calcium of (0.16 ± 0.049 mmol/l). Treatment duration varied from a single dose treatment to 5 years.…”

“…Four articles describe cohorts treated with a range of bisphosphonates. Three long-term treatment regimens ( 45 , 47 , 48 ), and one short term ( 46 ). The short-term study describes the use of bisphosphonates in pretreatment of patients undergoing parathyroidectomy and claims that bisphosphonate treatment can prevent development of hungry bones syndrome [although the number of patients treated is very limited ( n = 6)].…”

Skeletal Manifestations of Hyperparathyroidism

“…Lee et al reported the can prevent hungry bone syndrome among a very small number of patients [104]. Two other studies reported increase in BMD in the lumbar spine and hip [85,106].…”