Risk factors for development of atypical femoral fractures in patients on long-term oral bisphosphonate therapy

Paola Franceschetti; Marta Bondanelli; Gaetano Caruso; Maria Rosaria Ambrosio; Vincenzo Lorusso; Maria Chiara Zatelli; Leo Massari; Ettore C Degli Uberti

doi:10.1016/j.bone.2013.07.010

Risk factors for development of atypical femoral fractures in patients on long-term oral bisphosphonate therapy

Bone. 2013 Oct;56(2):426-31. doi: 10.1016/j.bone.2013.07.010. Epub 2013 Jul 17.

Authors

Paola Franceschetti¹, Marta Bondanelli, Gaetano Caruso, Maria Rosaria Ambrosio, Vincenzo Lorusso, Maria Chiara Zatelli, Leo Massari, Ettore C Degli Uberti

Affiliation

¹ Section of Endocrinology, Department of Medical Sciences, University of Ferrara, Via Savonarola 9, 44121 Ferrara, Italy. p.franceschetti@ospfe.it

PMID: 23871850
DOI: 10.1016/j.bone.2013.07.010

Abstract

Bisphosphonates (BPs) are the first-line therapy for osteoporosis. In recent years, atypical femoral fractures (AFF) have been described in patients on BPs therapy. However, the relationship between BPs and AFF remains to be clarified. We evaluated clinical and hormonal characteristics of AFF patients, in order to determine AFF risk factors. We studied 11 females with AFF and 58 females with typical femoral fractures (TFF), admitted to our Department for surgical repair between January 2008 and December 2011. All AFF patients received BPs therapy for 6 to 13 yrs, whereas 36.2% (p<0.0001) of TFF patients received BPs for shorter period (TFF, 6.1±1.8 yr vs. AFF, 8.6±1.9 yr, p<0.0001). A higher prevalence of hypocalcemia was observed in AFF patients compared with TFF (p<0.02), with significantly (p<0.05) lower corrected calcium levels in AFF patients. By contrast a reduced prevalence of elevated PTH levels (p<0.05) was found in AFF patients. No significant difference in prevalence of vitamin D defect was observed between the two groups. Younger age (p<0.004), higher BMI (>30 kg/m2, p<0.03) and early menopausal age (p<0.05) were observed in AFF patients. At time of fracture, prevalence of osteopenia/osteoporosis and levels of bone turnover markers were significantly (p<0.01) lower in AFF compared with TFF patients. By multivariate analysis hypocalcemia, obesity, and younger age (<70 yr) were confirmed to be independent predictors of AFF; elevated PTH level was the predominant independent protective factor (p<0.004). In conclusion, our data indicate that clinical characteristics and metabolic factors may favor the development of AFF in BP treated patients. We identified hypocalcemia due to latent hypoparathyroidism as primary risk factor for AFF; age, obesity, early menopause, and BMD may also influence the development of AFF. An adequate clinical and metabolic assessment is suggested to prevent the development of AFF in BP treated patients.

Keywords: Atypical femoral fractures; Bisphosphonate; Hypocalcemia; Hypoparathyroidsm.

MeSH terms

Aged
Aged, 80 and over
Bone Density Conservation Agents / adverse effects*
Bone Density Conservation Agents / therapeutic use
Diphosphonates / adverse effects*
Diphosphonates / therapeutic use
Female
Femoral Fractures / chemically induced*
Humans
Male
Middle Aged
Osteoporosis / drug therapy

Substances

Bone Density Conservation Agents
Diphosphonates