'Honest! My hip broke before I fell!'

Yes, this can indeed happen but infrequently and probably less often than that.

The patient is a 67-year-old overweight woman who experienced severe left hip pain about four years ago, and when she could no longer tolerate the pain after a few days an X-ray confirmed a fracture of the left proximal femur. She underwent a hip replacement. More recently she complained of right shoulder pain with exquisite local tenderness. Initial X-rays were not helpful but a CT and MRI confirmed a fracture through the spine of the scapula. A DXA was performed and to everyone’s surprise the T-score was –0.9 in the left hip and –0.3 in the lumbar spine. The 25-hydroxyvitamin D levels were near the upper limit of the reference interval (confirmed on three occasions), the parathyroid hormone level was in the middle of the reference interval (also confirmed). The serum calcium was 10.4 mg/dL (range 8.2-10.5 mg/dL) and was not flagged as abnormal, and on repeat was 10.1 mg/dL. Serum inorganic phosphate was 5.5 mg/dL (range 3.4-5.4 mg/dL).

Nine months before she was referred to me she was diagnosed with polymyalgia rheumatica and had immediate relief of symptoms when prednisone was started. Regrettably she has a recurrence of symptoms at doses of prednisone below 9 mg per day. Surprisingly, at least to me, her sedimentation rate never went below 70 and in fact changed little from the pre-prednisone level, despite marked symptomatic relief.

What is going on here? Spontaneous fractures can occur in patients on steroids, but her hip fracture had occurred several years earlier. Steroid therapy usually decreases bone density, but her values were normal. She did not have vitamin D deficiency, but perhaps she has primary hyperparathyroidism with her calcium consistently at the upper limit of normal.

It’s hard to conceive of even a minimal elevation of serum inorganic phosphate in primary hyperparathyroidism although it is the norm in patients with hyperparathyroidism secondary to chronic renal failure. Her estimated glomerular filtration rate was 47 and 53 on two separate occasions — renal impairment to be sure but not at a level where hyperphosphatemia might be expected.

The other ignored data was the serum alkaline phosphatase which was 17 IU on one occasion and 19 IU on repeat. The reference interval was listed as 0 to 150 and the abnormally low value was not flagged. The reference interval is incorrect and is more likely 40 to 150. Could she have adult onset hypophosphatasia? In my mind there was no acceptable alternative diagnosis but I have seen this genetic disorder rarely so I called the true authority — Michael Whyte, MD, professor of medicine at Washington University and Shriner’s Hospital in St. Louis. He agreed with my presumptive diagnosis and e-mailed the information needed to confirm the diagnosis by appropriate genetic testing. He also gave me permission to quote him in this blog, and the best way to do that would be to direct you to PubMed or another search engine and look for citations “Whyte M AND hypophosphatasia." Even a Google search that I did with the patient in the clinic came up with multiple references to the pioneering work Dr. Whyte has done on this condition and several other unusual and uncommon metabolic bone diseases.

My entry into the field of the clinical chemistry of metabolic bone diseases began as a medical student several decades ago when I had summer scholarship to work in the lab of Professor Sol Posen, the developer of the heat inactivation method for assessing the iso-enzymes for alkaline phosphatase. I worked in his lab for seven years and he remains my mentor and confidant to this day, but I am going to resist the temptation to go into details of the further work-up and management of hypophosphatasia here.

The purpose of this long blog is to re-state the importance of listening to the history, completing a physical examination and evaluating ALL data carefully. I can understand the consternation of finding a normal bone density in a patient with fragility fractures. But don’t just look for flagged abnormal labs, look carefully at all information available to you!