Phosphorus replacement, 'whole team' approach benefit patients with rare bone disorders
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Patients with both X-linked hypophosphatemia and tumor-induced osteomalacia can benefit from phosphorus replacement therapy, according to two presentations at the United Rheumatology Spring Virtual conference.
However, caution is warranted, as phosphorus can lead to gastrointestinal issues and other adverse events.
“XLH and TIO are rare progressive diseases resulting in multiple disabilities that affect the bones and muscles,” Suzanne Marie Jan de Beur, MD, associate director of the Johns Hopkins Bayview Clinical Research Unit, said in her presentation.
Both disorders involve upregulation of the protein fibroblast growth factor 23 (FGF23), chronic hypophosphatemia, increased renal phosphate excretion, dysregulated vitamin D metabolism, widespread osteomalacia and frequent fractures, according to de Beur, who focused primarily on TIO.
“You should have a high level of suspicion for TIO if you see someone who is weak, with pain and fractures,” de Beur said. Importantly, many of these patients are not old and were previously not frail or prone to pain or fractures.
Digging deeper into TIO, de Beur presented an overview of a typical case patient, a 56-year-old man who had a tumor under the first metatarsal in his foot. When the tumor was removed, this patient, like others who have their tumors removed, did “very well.”
“However, about 50% of the time we are not able to find the tumor right away,” de Beur said.
Even if the tumor is found, if it is abutted to a nerve or vasculature, it can be impossible to resect, de Beur added.
In these cases, medical therapy, largely in the form of phosphorus, is required. “You try to overcome biochemical deficits,” de Beur said.
The concerns with phosphorus therapy are many. Patients are required to take four to six doses per day. In addition, nephrocalcinosis, hypercalciuria and hyperparathyroidism, among other complications, may occur, according to de Beur. “It is not an easy medication,” she said. “It is not easy to manage long-term.”
With that in mind, denosumab (Prolia, Xgeva, Amgen) is a “promising” option to reduce FGF23 activity, according to de Beur. In addition, burosumab (Crysvita, Ultragenyx) binds to and inhibits FGF23. “Burosumab is a new possible approach to medical therapy in TIO,” she said.
The clinical presentation of a typical XLH patient is an individual with short stature, lower extremity deformity, joint pain and stiffness and a history of fractures, according to Nancy E. Lane, MD, director for the Center for Musculoskeletal Health at University of California, Davis.
“They can have extraosseous calcifications, enthesopathy and spinal stenosis,” she said. “Many of these complications would land this patient in a rheumatologist’s office.”
The source of the issue is in the PHEX gene, which is found in osteocytes, according to Lane. “This gene does not work well,” she said. Patients have too much FGF23, hypophosphaturia, hypophosphatemia, Ricketts and deformed bones. “Also, there can be tremendous muscle weakness.”
Patients may also have metabolic abnormalities or dental issues, according to Lane. These patients also have low serum phosphorus.
“Traditional [phosphorus] therapy is not particularly difficult, but it does take a bit of practice,” Lane said. In addition, vitamin D is recommended. “This is the one time giving active vitamin D is ok.”
Calcium supplements are not recommended, while nutritional vitamin D is recommended as long as it is “not too much,” according to Lane. As with TIO, burosumab is an emerging therapy for XLH patients that has been used with efficacy.
When treating a pediatric or young adult patient, enlisting the help of a pediatric endocrinologist may be necessary.
To that point, de Beur added that team care is optimal for both XLH and TIO patients, and may include an endocrinologist, rheumatologist, orthopedist, podiatrist and even a mental health professional.
“It takes a whole team to deliver the best care to these patients,” de Beur said.
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de Beur SMJ, Lane N. Improving XLH and TIO Disease Awareness and Differentiation Among Rheumatologists. Presented at: United Rheumatology Spring Virtual Conference; April 16-17, 2021.
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