Severely suppressed bone turnover and atypical skeletal fragility.
BACKGROUND
Since their introduction into clinical medicine, bisphosphonates have revolutionized clinical osteoporosis care. Ironically, in rare circumstances, long-term, combined anti-remodeling therapy may be associated with skeletal harm.


METHODS
We report atypical skeletal fragility in three subjects after long-term, combined anti-remodeling therapy.


RESULTS
Three subjects experienced spontaneous or minimal-trauma chalk-stick type metadiaphyseal femoral fractures while on long-term bisphosphonate therapy. The fracture location, type, bilaterality, prodromal pain, and delayed healing were atypical for uncomplicated postmenopausal osteoporosis. All three subjects had concomitant circumstances (endogenous estrogen) or medications (glucocorticoids, hormone replacement therapy, and raloxifene) that likely suppressed bone remodeling beyond the effect of the bisphosphonate alone. Biochemical markers of bone turnover were very low or in the low premenopausal range. Double tetracycline-labeled bone biopsy showed very low activation frequency in one subject and limited single tetracycline label in a second consistent with severely suppressed bone turnover (SSBT). These three cases resemble previous descriptions of SSBT.


CONCLUSIONS
Atypical skeletal fragility may signify SSBT in the setting of long-term, combined anti-remodeling therapy. We speculate that osteoclast tolerance for pharmacological suppression may vary among individual patients and that in some cases combined anti-remodeling therapy may result in skeletal harm.
Visekruna
Maja
M
Center for Bone Disease, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, Wisconsin 54449, USA. visekruna.maja@marshfieldclinic.org
Wilson
Deborah
D
McKiernan
Fergus Eoin
FE
D000368:Aged; D019386:Alendronate / Q000009:adverse effects*; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016723:Bone Remodeling / Q000187:drug effects*; D005260:Female; D005264:Femoral Fractures / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D013752:Tetracycline
D050071:Bone Density Conservation Agents; D013752:Tetracycline; D019386:Alendronate