What my colleagues are asking about skeletal health

How much vitamin D is enough? The only honest answer is that nobody knows for sure in an individual patient. A minimum of 1,000 units per day is needed, but doses up to 10,000 units per day appear to be safe. What is not clear is just how much a low level of 25-hydoxyvitamin D contributes to a patient who has a low bone density and whether replacing vitamin D has any measureable effect on bone density.

Patients with osteomalacia, even subclinical, should be easy to identify because the alkaline phosphatase will be elevated and the serum phosphate towards the low end of normal or frankly low. Additionally, 24-hour urine calcium excretion will be <100 mg and often <50 mg. Such patients need both vitamin D and calcium supplementation. If the serum calcium is also low, the osteomalacia has likely been missed for several years. As vitamin D levels fall, parathyroid hormone increases to maintain normal serum calcium at the expense of the skeleton. Patients with osteomalacia should not be given a bisphosphonate until the osteomalacia has healed. The last thing you want to do is to turn down the remodeling process!

Which bisphosphonate do I prefer? That’s easier to answer. There are to my knowledge no head-to-head clinical trials with anti-fracture effectiveness as the endpoint, and it is unlikely that there will be any anytime soon. Epidemiologic studies based on retrospective review of pharmacy databases and documentation of fracture from the medical record have attempted to answer this question, but all have shortcomings which are always discussed in the publications.

Head-to-head studies of the effect of different bisphosphonates on bone density are plentiful, but they are designed to demonstrate noninferiority, not superiority. All bisphosphonates work and work well. Your decision is most often based on the formulary of the patient’s insurance company, and you can do no wrong.

Daily, weekly, monthly, intravenously? It has been tough to find convincing data that the dosing interval has any impact on patient compliance with therapy. IV ibandronate (Boniva, Roche Laboratories; quarterly) or zoledronic acid (Reclast, Novartis; annually), would be expected to improve patient compliance, but these are still too new, particularly zoledronic acid, to be certain of this. One issue that bugs me is that IV ibandronate is designed for an IV push in the doctor’s office as opposed to an IV infusion in an infusion center (most often associated with an oncology program — not somewhere healthy patients want to visit for their preventive care) for zoledronic acid. Not many of us offer IV push in our practices, and the patient is forced to go to an infusion center which adds considerable cost and hassle. Convincing an infusion center to give an IV push is tough, again for obvious reasons.

One thing to remember — no osteoporosis therapy has been FDA approved until it has documented anti-fracture effectiveness in controlled clinical trials. This is, to my knowledge, a higher standard than drugs approved to control blood pressure or serum lipids.