Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy

Abstract

Bone remodelling suppressants like the bisphosphonates reduce bone loss and slow progression of structural decay. As remodelling removes damaged bone, when remodelling suppression is protracted, bone quality may be compromised predisposing to microdamage accumulation and atypical femoral fractures. The aim of this study was to determine whether teriparatide therapy assists in fracture healing and improves bone quality in patients with bisphosphonate associated atypical femoral fractures. A prospective study was conducted involving 14 consecutive patients presenting during 2 years with atypical femoral fracture. All patients were offered teriparatide therapy unless contraindicated. Age and sex matched control subjects without fragility fractures or anti-resorptive treatment were recruited. High resolution peripheral micro-computed tomography (HRpQCT) scans of the distal radius and distal tibia were analysed for their cortical bone tissue mineralisation density using new software (StrAx1.0, StrAxCorp, Australia) at baseline and 6 months after teriparatide. Administration of 20 μg of teriparatide subcutaneously daily for 6 months to 5 of the 14 patients was associated with 2-3 fold increase in bone remodelling markers (p=0.01) and fracture healing. At the distal radius, the proportion of less densely mineralised bone increased by 29.5% (p=0.01), and the proportion of older, more densely mineralised bone decreased by 16.2% (p=0.03). Similar observations were made at the distal tibia. Of the nine patients managed conservatively or surgically, seven had poor fracture healing with ongoing pain, one sustained a contralateral atypical fracture and one had fracture union after 1 year. Teriparatide may assist in healing of atypical fractures and restoration of bone quality.

PTH(1-34) Treatment Increases Bisphosphonate Turnover in Fracture Repair in Rats

“…PTH has been proposed as an intervention for recalcitrant AFFs and has already been used off-label clinically in several case reports and case series. (10,(15)(16)(17) PTH has also been used in the context of AFF in an individual with osteogenesis imperfecta, another condition associated with long-term bisphosphonate usage. (18) However, the capacity of PTH to remobilize BP in a fracture and the mechanism underlying improved healing remain unclear.…”

Use of teriparatide off-label: our experience and review of literature

“…In 2012 a prospective study was conducted involving 14 consecutive patients presenting during 2 years with atypical femoral fracture. Administration of 20 μg of teriparatide subcutaneously daily for 6 months to 5 of the 14 patients was associated with 2-3 fold increase in bone remodeling markers and fracture healing (28). In 2011, a prospective randomized controlled study was published where PTH (1-84) administration determined in 21 patients, within a sample of 65 postmenopausal osteoporotic women suffering from pelvis fracture, a faster repair with an improvement in functional outcome (29).…”

Heterogeneidade na apresentação clínica de fraturas atípicas após uso prolongado de bisfosfonatos – Fatores de risco e marcadores de remodelação óssea

“…A administração intermitente de altas doses de teriparatida aumenta o volume do calo ósseo após 20 e 40 dias de uso (28), age aumentando o remodelamento, re-movendo o osso antigo e supermineralizado, substituindo-o por uma nova matriz óssea e facilitando a consolidação óssea (9). Hansen e cols.…”