Approaches and treatments for the metabolic bone disorders rheumatologists are most likely to see, hypophosphatasia (HPP), osteomalacia (OM), and primary hyperthyroidism, are changing, and the outlook on all three is improving.
Persistent low alkaline phosphatase levels (less than 40) are the key to recognition of patients with HPP. The most common rheumatologic conditions associated with HPP include periarthritis, chondrocalcinosis, pseudogout, calcareous periarthritis of the shoulder, and diffuse idiopathic skeletal hyperostosis.
“This is something that should be on the radar for every rheumatologist,” said Chad Deal, MD, Head of the Cleveland Clinic Center for Osteoporosis and Bone Disease. “HPP had been thought of as a pediatric disease but it is now clear that mild cases may present in adulthood with either fractures or rheumatologic manifestations.”
Dr. Deal will kick off the Clinical Practice session Bad to the Bone: Metabolic Bone Disease from 2:30 – 4:00 pm Tuesday in the Thomas Murphy Ballroom 3 & 4, Building B in the Georgia World Congress Center. Not every rheumatologist focuses on metabolic bone disease, but these patients may be referred from primary care or other specialists for chondrocalcinosis or calcific periarthritis.
Hypophosphatasia can be a persistent problem, but one that finally has an approved treatment. The Food and Drug Administration approved asfotase alfa for perinatal-, infantile-, and juvenile-onset hypophosphatasia in 2015.
All patients with HPP have a genetic defect in the gene encoding tissue nonspecific alkaline phosphatase, Dr. Deal said. That means adult patients have actually had the disease since childhood. Even when HPP presents late in life, these patients will often have a history of premature loss of primary teeth before the age of five.
The cost of asfotase alfa is enormous and can easily be more than $1.5 million per year in adults. When, or even if, to begin treatment in a patient with mild disease is an important unanswered question.
“HPP is being recognized increasingly, at least in part because there is now a treatment,” Dr. Deal said. “And it is often overlooked simply because people don’t always notice a low alkaline phosphatase level on a comprehensive metabolic panel. High levels jump out, but low levels often go unnoticed and unevaluated.”
Osteomalacia is a mineralization defect. And while these patients have low bone mass, they are not treated with traditional medications used for osteoporosis. The most common cause of OM is severe vitamin D deficiency, which leads to secondary hyperparathyroidism with a high alkaline phosphatase.
Patients with OM often present with pseudo fractures, sometimes called Looser’s Zone. In advanced cases the patient may have a myopathy with normal CPK.
A common scenario is a patient who has had gastrointestinal surgery and lost a significant portion of the bowel and cannot absorb vitamin D from either diet or oral supplementation.
The standard treatment for these patients is high doses of vitamin D, Dr. Deal said. The response is often dramatic, with huge increases in bone density and increased muscle strength.
Patients referred for osteoporosis evaluation will sometimes have primary hyperthyroidism as the cause for low bone mass. The hallmarks are elevated parathyroid hormone (PTH) and elevated serum calcium.
There are published guidelines on when patients should be referred for surgical evaluation. Indications for referral include serum calcium more than 1mg/dl above normal, T-score <-2.5, vertebral fracture, GFR <60mL/min, 24 hours urine calcium >400mg/day, kidney stones, and age <50.
“Even if you don’t take care of metabolic bone disease in your practice, you need to recognize it so you can make the appropriate referrals,” Dr. Deal said. “This symposium will cover the nuts and bolts of evaluation and treatment that every rheumatologist needs to be aware of.”