Hypophosphatasia (HPP) is an ultra-rare metabolic bone disease caused by low levels of alkaline phosphatase in the body, resulting in poor mineralization—or a lack of it completely. Symptoms vary widely. Mild cases may only cause dental abnormalities, while severe cases can have life-threatening consequences. And dentists may find themselves on the front lines of diagnosing it.
“Alkaline phosphatase impacts mineralization and helps regulate the deposition of minerals like calcium and phosphorous during tooth development. Abnormal function can result in abnormal formation of the enamel, dentin, and root cementum, the three mineralized tissues of a tooth,” said Denise Goodbar, executive director of Soft Bones, a group for HPP patients that attends events such as the Greater New York Dental Meeting to promote awareness among dentists.
The Causes and Cases
HPP is caused by a faulty TNSALP or ALPL gene, which limits the body’s production of alkaline phosphatase. Without enough alkaline phosphatase, certain chemicals build up and prevent calcium and phosphorous from binding together, leading bones to be soft, curved, and fragile and teeth to become loose or fall out.
“It’s a genetic disease, so it’s a disease you have for your entire life,” said Goodbar. “I think there’s a misconception that it’s simply a childhood disease, when it’s not.”
Perinatal HPP is the most severe form of the disease, and life expectancy is measured only in days or weeks after birth. Infantile HPP isn’t fatal but still presents significant complications. Childhood HPP is less severe but may lead to developmental delays in sitting, crawling, and walking, with bowed legs or a misshapen skull or wrist and ankle joints possible. Plus, children with HPP may see their baby teeth fall out with their roots intact before the age of five.
Adult HPP typically isn’t diagnosed until middle age and can be confused with osteoporosis, with a similar risk of recurrent fractures. Odontohypophosphatasia, which is the most mild form of HPP, can affect both children and adults. Overall, HPP affects one in every 100,000 live births, though that number is difficult to determine.
“There’s so much misdiagnosis,” said Goodbar. “How many people are lost in this diagnostic odyssey? They’re told they have fibromyalgia, or they’re told they’re clumsy, because we have patients that their bones are so soft that they could get their foot caught in a sheet and roll over and break a bone.”
HPP frequently manifests in dental problems including decay and loss of teeth. Diagnosis of those oral health issues, however, may be tricky.
“There can be poor mineralization, so people can have teeth that break off. They can have more cavities. So in some ways, it can look like people aren’t following proper hygiene protocol, when in reality it’s a function of poor mineralization and underlying disease,” said Goodbar.
Treatment can be challenging as well. Though baby teeth are expected to fall out eventually, their early loss may impact future dentition. When adult teeth do come in, they may be soft or fragile, requiring careful or adapted use of tools like burs and drills. Orthodontists may need to take a similarly conservative approach.
“The dental professional that is taking care of the patient needs to look at the full picture because you might have to use different hardware. You might have to approach it a little bit differently than you would a traditional patient,” said Goodbar.
When adult teeth fall out, dentures and implants are potential treatment options. But aside from of maintaining and restoring teeth, clinicians also should understand how HPP takes a toll on quality of life. For example, such fragility overall can prevent patients from participating in physical activities like sports, while missing teeth can inhibit confidence and self-esteem.
Support System and Research
Soft Bones provides education about HPP as well as a community where patients and their families and caregivers can connect. In addition to its website and newsletter, it is on Facebook and Twitter, where people share their stories as well as advice and information. Plus, it hosts local and national meetings where patients and physicians can meet and engage with each other.
“Having an ultra-rare disease is very different from having a more common disease,” said Goodbar. “We all know people with diabetes. There are people with diabetes in our neighborhood. But hypophosphatasia is not like that. So to connect those patients, we host national meetings each year that bring families together so they can meet one another.”
Patient participation is vital to Soft Bones’ activities. It has a designated Region Lead in each of its eight coverage areas in the United States. These leads provide localized grassroots support to the Soft Bones community. They also have their “ears to the ground,” Goodbar says, and can elevate issues they find to the organization’s notice and identify materials that may benefit the entire community. The organization’s staff supports these volunteers.
Also, Soft Bones’ Physician Referral Network connects patients with providers who are familiar with HPP.
“We are working on building a dental referral list, just like we have a physician referral list. So, we’re looking for people who are interested in treating patients with hypophosphatasia,” said Goodbar.
Soft Bones also offers a registry where patients and caregivers can let researchers know that they are available for clinical trials. In June 2018, the organization conducted its first scientific meeting for a multinational group of 50 researchers, where they reviewed the current understanding of HPP and planned work for improving the lives of patients.
Also, Soft Bones has supported research by providing seven grants since its founding in 2008. One of these grants, a $25,000 award, went to Dr. Brian L. Foster of the College of Dentistry at Ohio State University. His work is the first study to quantitatively analyze teeth from a large group of HPP patients to gain a better understanding of how dental problems correlate with skeletal, biochemical, and genetic changes in such patients.
The organization’s work is guided by its Scientific Advisory Board, which includes physicians, endocrinologists, and other experts. It also includes Timothy Wright, MS, DDS, interim chairman of the Department of Endodontics at the University of North Carolina at Chapel Hill School of Dentistry and professor in its Department of Pediatrics.
“He’s very involved,” said Goodbar. “If I need help with a patient who is having a problem, I always reach out to him.”
Soft Bones advocates for public policy as well.
“We are also supporting the Ensuring Lasting Smiles Act, which is an act that’s out there right now that is looking to help people who are born with congenital anomalies and helping them get better care—maybe more frequent dental visits, et cetera—so private insurance would start to cover those treatments for those individuals impacted,” said Goodbar.
“We always say patient advocacy is a lot more than a t-shirt and a Facebook page. There’s a lot more that goes on beneath the surface that we’re really trying to teach and support the patient,” Goodbar said.
Finally, to complete this comprehensive community outreach, research, and advocacy, Soft Bones depends on grants and donations for funding. Goodbar says support is always welcome.
“If you’re interested in giving, we are happy to have donations,” Goodbar said. “We really survive on donations and grants, and we really focus a lot of our fundraising efforts on supporting our patients.”
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