Review ArticleSecondary Osteoporosis: A Review of The Recent Evidence
Section snippets
INTRODUCTION
Osteoporosis is a common disease, affecting about 4 to 6 million women and 1 to 2 million men in the United States (1). It increases a person’s risk for fractures and, thus, is associated with considerable morbidity and mortality. Although this disease most frequently affects postmenopausal women, it does not spare men or premenopausal women. Current therapies for osteoporosis can increase bone mineral density (BMD) and reduce fractures substantially. Nevertheless, correctable factors that
HYPOGONADISM
As previously noted, hypogonadism is one of the most common causes of osteoporosis in male patients. Testosterone and estrogen have roles in the maintenance of bone density. These hormones aid in bone formation and help prevent bone resorption (2,6., 7., 8.); interestingly, estrogen may have more of a role in halting bone resorption than does testosterone (7). Indeed, 70% of the gonadal effect on BMD in male subjects may be due to estrogen (7). This contribution of estrogen is being
MEDICATIONS
Numerous medications have been implicated in causing loss of BMD. Some of the most common offenders are immunosuppressants, heparin, and anticonvulsants. Most often, corticosteroids have been identified as a cause of osteoporosis (2,23). These drugs are used frequently—in 0.5% of one population examined (24). Even a relatively small dose can cause detrimental effects on BMD. One trial found that less than 2.5 mg of prednisolone per day was associated with an increased risk of fractures (25).
HYPERTHYROIDISM
Hyperthyroidism can cause osteoporosis as well, decreasing BMD by 10% to 30% in women (5). The cause of the hyperthyroidism does not seem to affect the degree of bone loss. Jodar et al (44), who compared the BMDs of patients with overt hyperthyroidism or controlled hyperthyroidism and healthy patients, found a decrease in BMD in those with overt hyperthyroidism or controlled hyperthyroidism in comparison with that in the healthy patients. In addition, the patients with overt hyperthyroidism had
VITAMIN D DEFICIENCY
Decreased vitamin D concentrations can have deleterious effects on bone metabolism. Two important metabolic bone derangements that can result from this situation are secondary hyperparathyroidism and osteomalacia. Secondary hyperparathyroidism develops when the vitamin D concentration decreases to an insufficient level (47). Consequently, evidence of increased bone turnover (47,48) and decreased BMD (48., 49., 50.) can be found. Lips (47) suggested that vitamin D insufficiency ranges from 10 to
PRIMARY HYPERPARATHYROIDISM
Primary hyperparathyroidism can cause decreased BMD, and it may increase the risk of fractures. This outcome is mainly attributable to an increase in bone resorption (49). PTH is likely catabolic in cortical bone, such as in the distal radius, and anabolic in cancellous bone, such as in the lumbar spine (63., 64., 65.). Thus, usually more cortical bone is lost than cancellous bone (49,63), although decreased density of cancellous bone has also been seen (63., 64., 65.). The correlation between
TRANSPLANTATION
Multiple factors contribute to the decline in BMD in patients with solid organ failure, as well as those who have received transplants. The disease itself, risk factors that develop because of the disease, and related medications, including loop diuretics and glucocorticoids, all contribute to the decreased BMD in such patients. Commonly, patients with end-organ failure are older, immobile, malnourished white subjects who have vitamin D deficiency or hypogonadism and who use tobacco or consume
GASTROINTESTINAL DISEASES
Various gastrointestinal diseases have been linked to osteoporosis, particularly inflammatory bowel disease and celiac sprue. Up to three-quarters of patients with inflammatory bowel disease may have decreased BMD (80). One study assessing 51 patients with Crohn’s disease and 40 patients with ulcerative colitis (UC) found that 55% of the patients with Crohn’s disease and 67% of those with UC had osteopenia, and 37% of the former group and 18% of the latter group had osteoporosis (81). Although
HEMATOLOGIC DISEASES
Several hematologic diseases, such as multiple myeloma, systemic mastocytosis, leukemia, and lymphoma, have been associated with decreased BMD (3). Of these, one of the most studied disorders is multiple myeloma. The main mechanism for the BMD loss in multiple myeloma is the synthesis of cytokines that activate osteoclasts by the plasma cells involved in this disease. Up to one-quarter of the patients with multiple myeloma can have low bone mass (3). Abrahamsen et al (89) found an increased
CUSHING’S SYNDROME
Elevated cortisol concentrations resulting from exogenous sources and endogenous production can adversely affect BMD (3). Numerous studies have evaluated the effect of endogenous hypercortisolism on the human skeleton. Normal subjects have exhibited a positive correlation between plasma cortisol concentrations and the rate of bone loss (91,92). Decreased BMD has been found in those patients with subclinical hypercortisolism (93). In patients with Cushing’s syndrome, a negative association
IDIOPATHIC HYPERCALCIURIA
Idiopathic hypercalciuria (IH) is found in more than half of the patients with recurrent renal stones (96). In addition to causing nephrolithiasis, IH is also associated with decreased BMD 97., 98., 99.. Studies have reported a decrease in BMD of up to 20% (98., 99.). IH causes bone loss by many mechanisms. First, patients have increased bone resorption, likely stimulated by cytokines. Misael da Silva et al (99) studied 40 patients with recurrent renal stones, subclassified into hypercalciuric
SCREENING
Various recommendations exist regarding when to search for secondary causes of osteoporosis. According to Stein and Shane (5), all women who have not entered menopause and all men who experience fragility fractures or have a Z-score of less than -1 should undergo further evaluation. Several approaches to this investigation have been proposed. For example, the aforementioned investigators have suggested that, in all patients with osteoporosis, a complete blood cell count, complete metabolic
CONCLUSION
Secondary osteoporosis is a common disease that affects patients who have not typically been considered at high risk for decreased BMD—namely, men and premenopausal women. It also contributes to low BMD in postmenopausal women, in whom, historically, classic primary osteoporosis is prominent. The causes of this disease are broad. We reviewed some of the more common etio-logic factors that have been discussed recently in the medical literature. Heightened awareness of the potential presence of
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