Third‐generation bisphosphonates for cochlear otosclerosis stabilizes sensorineural hearing loss in long‐term follow‐up

Abstract

ObjectiveTo assess long‐term hearing outcomes in patients treated with third‐generation bisphosphonates for otosclerosis‐related progressive sensorineural hearing loss (SNHL).Study DesignRetrospective case series reviewMethodsWe performed a retrospective case series review of patients with otosclerosis and progressive SNHL. Patients were treated with either risedronate or zoledronate after a diagnosis of otosclerosis with a significant SNHL component. Bone conduction pure tone threshold averages (BC‐PTAs) and word recognition scores (WRS) before and after bisphosphonate administration in long‐term follow‐up was analyzed. Significant change in BC‐PTA was defined as greater than 10dB or between 4% and 18% in WRS based on binomial variance.ResultsSeven patients were identified and 14 ears met inclusion criteria. Three patients were female and the mean age was 48.3 ± 10.3 years. The mean duration between treatment with bisphosphonate administration and long‐term post‐treatment follow‐up audiometry was 87.6 ± 18.3 months, with a range of 61.6 to 109.1 months and median of 89.2 months. Analysis using BC‐PTA and WRS demonstrated that 11 ears remained stable while 2 improved and 1 worsened. No patient experienced any major complication as the result of bisphosphonate therapy.ConclusionTreatment with third‐generation bisphosphonates is associated with stability in otosclerosis‐related sensorineural hearing over 5‐ to 9‐year period. These results suggest that such medications may prevent the progression of SNHL in patients with otosclerosis.Level of Evidence4 (Case series).

Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate

“…Moreover, these findings in mice supported the effect of zoledronate, which is approved for the treatment of osteoporosis and related bone diseases (Pazianas and Abrahamsen, 2011), as an off-label treatment in otosclerosis, a disease characterized by pathologic remodeling of the cochlear bone (Quesnel et al, 2012). Because word recognition is a sensitive metric of cochlear neural function, a surprising clinical observation (Quesnel et al, 2012;Jan et al, 2017) that bisphosphonates could stabilize SNHL and improve word recognition scores in patients with otosclerosis, together with our previous results on the influence of the drug on cochlear sensory cells (Kao et al, 2013), prompted us to assess the effects of bisphosphonates on cochlear synaptopathy.…”

“…This double-blind prospective study showed a non-significant trend toward hearing stabilization and improvement in the etidronate group compared to the placebo group ( Kennedy et al, 1993 ). In a 9-year follow-up study at our institution, patients with cochlear otosclerosis treated with the third-generation bisphosphonate zoledronate showed stabilization or improvement of SNHL and did not exhibit any side effects ( Jan et al, 2017 ). Despite the broad use of bisphosphonates, there are only three reported cases of ototoxicity after etidronate or pamidronate therapy ( Reid et al, 1995 ; Yasil et al, 1998 ).…”

Bisphosphonate therapy in otosclerosis: A scoping review

“…The other studies utilizing the same subject population were two double-blind RCTs by de Oliveira Vicente et al in 2012 12 and 2015. 13 Unlike the Jan et al 14 The treatment period was 6 months. The 2012 report compared air and bone conduction thresholds, air bone gap, speech recognition threshold, and speech discrimination between groups and within each group pre-and post-treatment.…”

“…One pair of linked studies includes the study from Jan et al, 14 which is a long-term follow-up of Quesnel et al rate of change in disease progression in the year just prior to the experiment (1-year pretreatment data) as well as the overall progression (first available data). Both the 2012 and 2017 studies used a ±10 dB as a significant change in bone conduction thresholds.…”

Osteoporosis, bisphosphonate use, and risk of moderate or worse hearing loss in women

“…A double‐blind clinical trial found a nonsignificant trend toward stabilization or improvement in air conduction thresholds at 1 and 4 kHz after treatment with etidronate 14 . A small study of patients with otosclerosis and progressive hearing loss before treatment was suggestive of stabilization of hearing thresholds and word recognition scores after zoledronate treatment, but there was no control group for comparison 44 . A promising study in noise‐exposed mice found zoledronate reversed noise‐induced damage to primary afferent auditory synapses and subsequent recovery of peripheral auditory function.…”