Hypophosphatasia, a genetic disorder characterised biochemically by low activity of alkaline phosphatase (BAP) and high levels of phosphate esters including pyridoxal 5-phosphate (PLP), is associated with mineralisation defects and subtrochanteric femoral fractures. The latter suggest that bisphosphonates (BPs) should be avoided in patients with adult-onset hypophosphatasia as bisphosphonates might further inhibit alkaline phosphatase activity by binding zinc and magnesium. The aim of the study was to determine the effect of BPs on PLP levels. Ninety-two women with postmenopausal osteoporosis (> 5 years since menopause, < 85 years old) were randomized to treatment for two years with one of three amino-bisphosphonates, alendronate (70 mg weekly, n=33), ibandronate (150 mg monthly, n=28) or risedronate (35 mg weekly, n=31) as well as supplemental vitamin D and calcium. A control arm comprised 21 healthy women aged 35-40 who remained untreated for 2 years. We measured BAP (iSYS, IDS) and PLP (HPLC, normal<100) at baseline and 2 years and show the geometric means (and 95% confidence intervals) in the table:
|BAP, ng/mL||BAP, ng/mL||PLP, nmol/L||PLP, nmol/L|
|Baseline||2 years||Baseline||2 years|
|Osteoporosis||18.9 (17.4-20.4)||10.8 (10.1-11.6)||63 (56-70)||57 (51-65)|
|Controls||9.6 (8.1-11.2)||10.1 (9.2-11.2)||63 (48-83)||68 (52-89)|
There was a 43% decrease in BAP (p<0.001) in the osteoporotic women treated with bisphosphonate, but no change in the controls. There was no change in PLP in either group. A 78-year old woman treated with alendronate for an extra 3 years developed an atypical fracture of the left femoral shaft from among the 92 women and she had a normal initial PLP (75 nmol/L) and this was unchanged (67) after two years. We conclude that amino-bisphosphonate therapy in osteoporosis patients has no effect on the hydrolysis of phosphate esters by alkaline phosphatase.
Disclosure: Dr N Peel has received speakers honoraria and funding from Warner-Chilcott. Dr Walsh has received speakers honoraria. Professor McCloskey has received funding from Warner-Chilcott. Professor Eastell has received funding from Warner-Chilcott and the NIHR and consultancy funding from Warner-Chilcott, Roche, Immunodiagnostic Systems and Merck.