The detrimental effect of aminohydroxypropylidene bisphosphonate (APD) in otospongiosis

Boumans, L.J.J.M.; Poublon, R. M. L.

doi:10.1007/bf00173660

Cited by 15 publications

(5 citation statements)

References 5 publications

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“…A uditory ossicles in the middle ear—the malleus, incus, and stapes—are highly mineralized bones

^{(^{(1)})}

that transmit sound in a chain from the tympanic membrane to the cochlea of the inner ear.

^{(^{(2)})}

These ossicles are excessively resorbed in the course of middle ear diseases such as cholesteatoma and chronic otitis media, both of which can result in hearing loss.

^{(^{(3)})}

Enhanced osteoclast formation in middle ear diseases is explained in part by increased production of osteoclastogenic pro‐inflammatory mediators. Ossiculoplasty can be performed to replace damaged auditory ossicles with synthetic ossicles composed of ear lobe cartilage, titanium, or other materials.

^{(^{(4)})}

In addition, antiresorptive therapy has been considered for middle ear diseases such as otosclerosis and cholesteatoma.

^{(^{(5–7)})}

…”

Section: Introductionmentioning

confidence: 99%

Bisphosphonate Therapy Ameliorates Hearing Loss in Mice Lacking Osteoprotegerin

Kanzaki

Takada

Ogawa

et al. 2009

Journal of Bone and Mineral Research

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Three auditory ossicles including the malleus, incus, and stapes conduct sound in the middle ear from the tympanic membrane to the inner ear. Auditory ossicles are massively resorbed by osteoclasts in Opg −/− mice, which lack osteoprotegerin (OPG), a soluble decoy receptor for the osteoclastogenic cytokine RANKL. Opg −/− mice exhibit progressive hearing loss and are a model for juvenile Paget's disease. However, effects of antiresorptive treatment on auditory ossicles and on hearing function in Opg −/− mice are unknown. We intraperitoneally injected Opg −/− mice with bisphosphonate risedronate 5 d/wk for 9 wk. Morphology of auditory ossicles was examined microscopically, radiographically, and histologically. Hearing function was monitored by measuring the auditory brain stem response (ABR). Control Opg −/− mice exhibited thinning of all three ossicles and tibia. In contrast, risedronate treatment significantly inhibited bone loss in auditory ossicles as well as in long bones of Opg −/− mice. Bony fusion of the junction between the stapes and the otic capsule was reduced after treatment. Moreover, ABR measurement showed that hearing in Opg −/− mice was significantly improved by risedronate treatment. These data suggest that hearing loss in pathologies characterized by excessive resorption of the auditory ossicles may be prevented by bisphosphonates.

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“…A uditory ossicles in the middle ear—the malleus, incus, and stapes—are highly mineralized bones

^{(^{(1)})}

that transmit sound in a chain from the tympanic membrane to the cochlea of the inner ear.

^{(^{(2)})}

These ossicles are excessively resorbed in the course of middle ear diseases such as cholesteatoma and chronic otitis media, both of which can result in hearing loss.

^{(^{(3)})}

^{(^{(4)})}

In addition, antiresorptive therapy has been considered for middle ear diseases such as otosclerosis and cholesteatoma.

^{(^{(5–7)})}

…”

Section: Introductionmentioning

confidence: 99%

Bisphosphonate Therapy Ameliorates Hearing Loss in Mice Lacking Osteoprotegerin

Kanzaki

Takada

Ogawa

et al. 2009

Journal of Bone and Mineral Research

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“…( 27 ) In adult Paget's disease, there is no convincing evidence that treatment improves hearing in patients with skull involvement, ( 28 ) and there has also been concern that bisphosphonates can worsen deafness in stapedial otosclerosis. ( 29 ) Our patient is the first with IH to have a documented improvement in audiometry with treatment. The improvement was modest, and greatest at low frequencies.…”

Section: Discussionmentioning

confidence: 64%

Treatment of Idiopathic Hyperphosphatasia With Intensive Bisphosphonate Therapy

Cundy

Wheadon

King

2004

Journal of Bone and Mineral Research

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In a family with IH, a rare high turnover bone disease, two older siblings were wheelchairbound with severe skeletal deformity by age 15. Their youngest affected sibling was treated intensively with intravenous bisphosphonates for 3 years. The treatment was well tolerated and prevented the development of deformity and disability.Introduction: Idiopathic hyperphosphatasia (IH, also known as juvenile Paget's disease) is a rare genetic bone disease characterized by very high bone turnover and progressive bony deformity. Inhibitors of bone resorption have been used to suppress bone turnover in the short term, but there is no published data on long-term efficacy. Materials and Methods: An 11-year-old girl with IH, who had two severely affected older siblings, presented with progressive deformity and deafness and long bone fractures. Conventional pediatric doses of pamidronate had failed to prevent clinical deterioration or suppress bone turnover completely. Intensive bisphosphonate therapy (frequent 5-mg ibandronate infusions) was given to try and arrest progression of the skeletal disease. Growth and development, pure tone audiometry, biochemistry, radiology, densitometry (DXA), and bone histology were monitored. Results: A total of 45 mg ibandronate was given over 3 years until skeletal maturity was reached (20, 15, and 10 mg for years 1-3, respectively). Ibandronate treatment was well tolerated, and biochemical markers of bone turnover suppressed to within the age-appropriate normal range There was some progression of her thoracic kyphosis, but she had no further fractures and remained mobile and active at an age when her siblings had become wheelchair-bound. A significant recovery of hearing (p Ͻ 0.01) was documented, particularly at low frequencies. Radiographs showed improvement in spinal osteoporosis and cortical bone dimensions and arrest of progressive acetabular protrusion. Areal bone density increased substantially (lumbar spine z-score from Ϫ2.2 to ϩ 1.8). Tetracycline-labeled bone biopsy specimens were taken before and after 18 months of intensive treatment. The second biopsy showed suppression of bone turnover and a doubling of trabecular thickness, with no mineralization defect, and no osteopetrosis. Conclusions: Intensive bisphosphonate treatment prevented the development of deformity and disability and improved hearing in this child with IH. The dose of bisphosphonate, which is substantially greater than is usually used in pediatric bone disease, had no adverse effects, in particular on bone mineralization.

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“…There is a dearth of clinical evidence demonstrating improved hearing or halted hearing loss in human subjects, and this scoping review shows the scarcity of available research. Basic science research with animal studies, [17][18][19] cadaveric studies, 20 case studies, 21,22 and reports are currently the most available type of research evidence.…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonate therapy in otosclerosis: A scoping review

Zimmerer

Africa

Westenhaver

et al. 2022

Laryngoscope Investig Oto

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Objective: Otosclerosis, a leading cause of deafness in adults, results from defective bone remodeling of the otic capsule. Bisphosphonates have been used to decrease bone remolding in many diseases, including otosclerosis. This study analyzes whether current literature supports bisphosphonate therapy as an effective treatment for otosclerosis.Design: Scoping review.Methods: A search was performed in three electronic databases; PubMed, Scopus, and Cochrane Control Trials. Articles were screened independently by two masked reviewers based on prespecified inclusion and exclusion criteria. After unmasking, the two reviewers resolved discrepancies through discussion.Results: From the search, 35 unique articles were identified for analysis. The dates of these publications range from 1982 to 2018. Further title and full-text review identified six articles for inclusion in this review. Three of the studies included are randomized controlled trials (RCT)s, and three are retrospective case reviews. These studies analyzed bisphosphonate therapy regimens, but dose and study length varied, making direct comparisons difficult. Only one RCT study was able to show a statistically significant change between patients treated with bisphosphonates compared to a control group. Conclusions:The efficacy of bisphosphonates for halting bone remodeling in otosclerosis remains unclear. Reviewing the literature, we found significant variations in experimental design and few studies of high-level evidence. Future RCTs investigating therapies for otosclerosis are needed before a firm conclusion about bisphosphonates efficacy as a pharmacological treatment of otosclerosis.

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The detrimental effect of aminohydroxypropylidene bisphosphonate (APD) in otospongiosis

Cited by 15 publications

References 5 publications

Bisphosphonate Therapy Ameliorates Hearing Loss in Mice Lacking Osteoprotegerin

Bisphosphonate Therapy Ameliorates Hearing Loss in Mice Lacking Osteoprotegerin

Treatment of Idiopathic Hyperphosphatasia With Intensive Bisphosphonate Therapy

Bisphosphonate therapy in otosclerosis: A scoping review

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