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Too much of a good thing
Not everything that is ‘good for you’ is good for bone health.
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A 63-year-old white man with a recent right-sided heel fracture was referred to me by his podiatrist. Testing for bone mineral density had demonstrated a T score at the lumbar spine of –4 with a Z score of –3.7. T scores for femur and radius were in the osteopenic range at –1.9. While he initially denied a history of other fractures, he later recalled that he had a stress fracture of the right second metatarsal bone many years ago. He denied a history of kidney stones. When prompted, the patient reported a loss of height of more than 1 inch over the past decades.
He also stated that he had a positive family history of osteoporosis, since his father had suffered an osteoporotic hip fracture. The patient furthermore stated that he was drinking skim milk with his coffee and eating cheese once a week. He was staying out of the sun and using sunscreen. He was a non-smoker and had one to two glasses of wine per day. He never lived through a period of starvation and reported normal development as a child through puberty. While the patient did not take any vitamin D supplements, he did take calcium carbonate 600 mg twice a day. He stated that he shaved daily and had reasonably good libido, along with moderate erectile dysfunction (SHIM score was 16 out of 25).
Past medical history was remarkable for bilateral heel spurs, colon polyps, Schatzki’s ring, gastrointestinal reflux disease, androgenetic alopecia, and tonsillectomy.
Medications included calcium carbonate, finasteride, lansoprazole, sildenafil as needed, multiple supplements including glucosamine chondroitin, ‘booster pills’ for hair growth, as well as Rhodiola, a multivitamin and vitamin B1, as well as several other supplements, the name of which he could not recall at the time of the initial visit.
On physical examination, this was a normal-weight anxious white man, 71 in, 180 lb, afebrile, heart rate 59, and BP 110/60 mmHg. The thyroid gland was mildly enlarged, smooth, and nontender. There was no bone tenderness. Full exam, including urogenital examination, otherwise unremarkable.
Abnormal labs: 24h urine N-Telopeptide elevated at 91, Vitamin D25(OH) mildly low at 26, estradiol mildly elevated at 41. Normal labs: comprehensive metabolic profile, urine calcium, serum phosphorous, calcium, serum and urine electrophoresis, dehydroepiandrosterone sulfate, vitamin D1,25(OH), testosterone profile and thyroid-stimulating hormone. Skeletal survey of the complete spine was without fractures, but the radiologist commented on noticeable osteopenia visible on X-ray.
Other than supplementing this patient with vitamin D and calcium, encouraging moderation in alcohol intake, and recommending bisphosphonate treatment, what is the best course of action?
- Send the patient to Alcoholics Anonymous. This patient’s alcohol intake is the primary cause of his osteoporosis. Once he is completely abstinent, his BMD will increase to normal levels.
- Have the patient call you back with a complete list of all his nutritional supplements.
- Stop this patient’s proton pump inhibitor.
- Start testosterone gel 1%, 5 g daily for hypogonadism.
- To strengthen the skeletal apparatus, you recommend weight-bearing exercises, in the form of weight-lifting, at least 150 lb times 12 repetitions, in sets of three.
CASE DISCUSSION
This otherwise rather healthy patient was in deep distress due to his poor BMD and maintained that he was not exceeding two glasses of wine per day. While chronic alcohol abuse is indeed associated with decreased BMD, mild to moderate drinking has been shown to correlate with mildly increased BMD.
 Ronald Tamler |
If one is to take this patient by his word, option A therefore does not represent the best course of action. Proton pump inhibitors are indeed on the list of agents that are associated with decreased BMD, probably due to decreased calcium absorption. Patients using these agents, which are now available over the counter and may not be perceived as “real” medications anymore, should be supplemented with calcium citrate, not calcium carbonate, for that reason. However, Lansoprazole cannot be held responsible for such a significant decline in BMD, and the patient’s reflux disease would become noticeable very quickly were he to stop his proton pump inhibitor (option C). This patient does indeed have moderate erectile dysfunction, but it would be inappropriate to assume that he is therefore hypogonadal, especially in the setting of no other hypogonadal symptoms and a normal testosterone profile (D). Finally, while weight-bearing exercises have beneficial effects on BMD, overdoing it may cause harm in this patient with severe osteoporosis of the spine (E).
I asked the patient to call me back when he got home and list all his supplements, along with a list of ingredients. It turned out that for years, he had been taking multiple vitamin supplements and was taking (all multivitamins combined) about seven times the recommended daily allowance for vitamin A (3,000 U) and about twice the tolerable upper intake level daily (source: ods.od.nih.gov). Indeed, vitamin A levels and the ratio of vitamin A and retinol-binding protein were elevated in this patient, once measured. I therefore instructed him to discontinue all supplements with vitamin A or retinol. Vitamin A intoxication can be the cause of increased osteoclast activity and osteoporosis, and even an intake of just twice the RDA may decrease BMD and increase fracture risk. As a fat-soluble vitamin, it can be stored and accumulate in the body. Ironically, chronic vitamin A intoxication can also accelerate hair loss … maybe this patient could have saved on the finasteride?
Ronald Tamler, MD, PhD, is an Assistant Professor in the Division of Endocrinology at Mount Sinai School of Medicine.