Home is where the heart is. The buildings we live in are much more than the structural features that protect residents and their belongings. Likewise, the bone that houses the ear provides more than structure and protection to the intricate machinery that allows us to hear. The bone of the ear is highly specialized and different from every other bone in the body. Scientists now recognize that these unique features of ear bone not only afford exquisite packaging, but also are critical to our ability to hear.
Ear Bone Is Unique
Each bone in the skeleton has unique properties that are thought to enable its specifi c function. It should then come as no surprise that bone of the ear has highly specialized properties. The entire ear is embedded within the temporal bone of the skull. The bone is an important architectural and functional component of the outer, middle and inner ear. The bony canal of the outer ear permits sound waves to enter the ear. The sound waves vibrate the eardrum, which is connected to the bones of the middle ear. These three bones, the smallest bones in the body, are responsible for transmitting sound energy to the cochlea. They are well known for their distinctive shapes that resemble a hammer (the malleus), an anvil (the incus) and a stirrup (the stapes). Their small size and unique geometry facilitate the amplifi cation of sound waves before they enter the cochlea. The cochlea houses all of the sensory and neural structures of the ear that convert sound into nerve impulses. This sensorineural infrastructure is encased in a bony covering that on the outside resembles a snail shell.
In addition to their characteristic sizes and shapes, ear bones are the hardest bones in the body. This is based on studies of whale ear bone and on clinical observation. How the hardness of ear bone is established and the importance of these physical properties for hearing are not known. By applying tools and approaches that are more commonly used in engineering, scientists are refining our understanding of the “mechanics” of ear bone and its role in hearing.
The ear bone is also unique because it does not undergo normal skeletal remodeling. Just as one remodels a house, the skeleton is remodeled every 10 years to accommodate changes in growth, weight, sexual maturity, physical activity or nutrition. Cells called osteoclasts degrade old bone to make way for the new bone deposited by osteoblasts, their partners in remodeling. The dynamic process by which old bone is destroyed and replaced by new bone allows for repair of microscopic cracks that accumulate over time. However, bone in the healthy ear has few osteoclasts and remodels very little or not at all. This has important implications for the ear.
The cochlea of a newborn is nearly full grown. In addition, injured ear bones do not regenerate as effectively as fractures in other parts of the skeleton. With these apparent disadvantages, why would the ear not undergo this otherwise normal remodeling? We don’t know the answer, but the privileged status of cochlear bone is clearly important because when cochlear bone does remodel, hearing loss may result.
Hearing Loss Associated with Bone Diseases
Bony abnormalities can cause both conductive and sensorineural hearing loss, the two major classifications of hearing loss. Infections, obstructions, traumatic injury or bony malformations in the outer or middle ear can block the conduction of sound into the inner ear and are classifi ed as conductive defects. In rare bone diseases, bony overgrowth compresses the cranial nerves that carry auditory signals to the brain. Loss of function in these nerves, due to such bony abnormalities, is classified as sensorineural hearing loss. In addition, a number of bony abnormalities cause loss of both conductive and sensorineural hearing function and are sometimes classified as mixed hearing loss. For several of these, the reason that bony defects result in a loss of sensorineural hearing function remains a mystery.
Paget’s disease results from abnormal remodeling of bone and can affl ict any site in the skeleton. When bones in the cochlea remodel due to Paget’s disease, conductive and sensorineural hearing loss is the result. Ear bone remodeling is also associated with otosclerosis and can impact the cochlea and cause both conductive and sensorineural hearing loss. Bone remodeling can alter the cochlear structure and function, yet even in the absence of such changes, sensorineural hearing loss can occur. A number of rare genetic bone syndromes, including osteogenesis imperfecta and cleidocranial dysplasia, are also associated with sensorineural hearing loss even in the absence of apparent anatomical or microscopic defects in the ear. Though cleidocranial dysplasia can be accompanied by bony malformations in many cases, the way that bone disrupts sensorineural hearing is not well understood.
Currently, most bone disease-associated hearing loss is treated with either bisphosphonates or fluoride. These drugs integrate into bone matrix to block bone destruction by osteoclasts. This prevents bone loss and, in turn, the pathological remodeling of cochlear bone that is apparent in several bone diseases, including Paget’s disease, cochlear otosclerosis and osteogenesis imperfecta. Bisphosphonates are the most commonly prescribed drug for osteoporosis. Interestingly, fluoridation of water has coincided with a striking reduction in the incidence of otosclerosis. Though highly effective in preventing fracture and pain at other skeletal sites in osteoporosis, the extent to which bishosphonates improve hearing is not so well-established. Some studies show improvement in hearing whereas others do not. The relative rarity of these diseases makes large-scale clinical studies difficult.
Even more problematic is that we know little about how changes in bone directly impact sensorineural ear function. The ability to understand how increased remodeling of the cochlear bone results in loss of sensorineural function has been limited, until recently, by the availability of suitable experimental model systems.We are now seeing important scientific progress in this area that may lead to the development of new drugs that can prevent hearing loss associated with some of these diseases.
Potential Causes of Hearing Loss
Although much remains to be determined about the mechanisms by which defects in bone cause
hearing loss and how to prevent it, previous studies provide several attractive possibilities. With the application of genetic mouse models, state-of-the-art scientifi c instrumentation and high-resolution imaging, solving these mysteries is more feasible than ever before. Understanding how bony defects cause sensorineural hearing loss will open novel avenues for therapeutic intervention.
Recent studies with genetically modifi ed mice have made major strides in understanding the role of cochlear bone remodeling in hearing loss. These studies have led to the identifi cation of the protein responsible for the absence of bone remodeling in normal cochlear bone. This protein, called osteoprotegerin, inhibits osteoclast formation and function and has exciting therapeutic potential as a target for new biological or pharmaceutical drug development.
Additionally, studies are exploring a number of ways that abnormal bone remodeling has the potential to upset normal cochlear function. First, the sensorineural cells of the cochlea are in intimate proximity to the underlying bone. Remodeling of the bony substrate may impair normal structure and function of these sensorineural structures.
Second, remodeling of cochlear bone may disrupt the fragile biochemical balance of the cochlea. Bone remodeling releases large quantities of mineral and growth ear could compromise hearing. Growth factors released from bone could also disrupt normal sensorineural cochlear cell function or recruit infl ammatory cells to the cochlea that further propel the disease state.
A third possibility couples the lack of cochlear bone remodeling to the hardness of cochlear bone. Typically, the least remodeled bones have the highest mineral content. The most mineralized bones are often the hardest. Increases in bone remodeling in Paget’s disease that cause hearing loss have been associated with reduced cochlear bone mineral content, as measured using CT scans. Therefore, the unique hardness of the ear bone may be related to the absence of cochlear bone
remodeling, which together may be essential for normal hearing.
Current research is elucidating the unique features of bone in the ear, how these features are established and what the contribution of ear bone is to normal hearing. It is clear that the role of bone in the ear extends beyond providing a pathway through which sound is transmitted, or simply a protective coating for the delicate structures of the inner ear. Several scientific and technological breakthroughs now give scientists an opportunity to identify the mysterious causes of sensorineural hearing loss in rare bone diseases. While directly benefi ting those with bone disease-associated hearing loss, these answers may reveal unexpected ways that bone participates in other forms of hearing loss and may spark the development of new bone-directed therapies to improve hearing.
