Alendronate, an inhibitor of bone resorption, is widely used in osteoporosis treatment. However, concerns have been raised about potential oversuppression of bone turnover during long-term use. We report on nine patients who sustained spontaneous nonspinal fractures while on alendronate therapy, six of whom displayed either delayed or absent fracture healing for 3 months to 2 yr during therapy. Histomorphometric analysis of the cancellous bone showed markedly suppressed bone formation, with reduced or absent osteoblastic surface in most patients. Osteoclastic surface was low or low-normal in eight patients, and eroded surface was decreased in four. Matrix synthesis was markedly diminished, with absence of double-tetracycline label and absent or reduced single-tetracycline label in all patients. The same trend was seen in the intracortical and endocortical surfaces. Our findings raise the possibility that severe suppression of bone turnover may develop during long-term alendronate therapy, resulting in increased susceptibility to, and delayed healing of, nonspinal fractures. Although coadministration of estrogen or glucocorticoids appears to be a predisposing factor, this apparent complication can also occur with monotherapy. Our observations emphasize the need for increased awareness and monitoring for the potential development of excessive suppression of bone turnover during long-term alendronate therapy.

Long-term bisphosphonate therapy may increase the risk of unusual long bone mid-shaft fractures. This is probably due to prolonged suppression of bone turnover, which could lead to accumulation of microdamage and development of hypermineralized bone. At present, the scope of this complication in the larger context of patients receiving bisphosphonate therapy remains unknown, but appears to be small.

Foods that are high in citrate content generally are assumed to deliver alkali load when consumed irrespective of the accompanying cation. The object of this randomized, crossover study was to compare the effects of orange juice with those of lemonade on acid-base profile and urinary stone risks under controlled metabolic conditions. Thirteen volunteers (nine healthy subjects and four stone formers) sequentially received distilled water, orange juice, or lemonade while on constant metabolic diet. Twenty-four-hour urine samples were collected for acid-base parameters and stone risk analysis. Orange juice but not lemonade provided alkali as evidenced by higher net gastrointestinal alkali absorption and higher urinary pH and citrate compared with control. Urinary calcium was not significantly different, but urinary oxalate was higher during the orange juice phase. The calculated supersaturation of calcium oxalate was lower in the orange juice phase compared with control. Calculated undissociated uric acid was lower in the orange juice phase compared with both control and lemonade phases. The calculated supersaturation of brushite was significantly higher in the orange juice phase compared with both control and lemonade phases. Despite comparable citrate content, this study showed that orange juice has greater alkalinizing and citraturic effects than lemonade. Consumption of orange juice was associated with lower calculated calcium oxalate supersaturation and lower calculated undissociated uric acid. This short-term study suggests that orange juice consumption could result in biochemical modification of stone risk factors; however, additional studies are needed to evaluate its role in long-term prevention of recurrent nephrolithiasis.Clin J Am Soc Nephrol 1: 1269 -1274, 2006. doi: 10.2215/CJN.00800306 M anagement of recurrent kidney stones requires both diet/lifestyle modification and medical therapy, and one of the important elements of medical therapy is the administration of potassium alkali such as potassium citrate. Potassium citrate has been shown to decrease stone formation rate in patients with idiopathic hypocitraturic calcium nephrolithiasis (1,2), hyperuricosuric (3), and thiazideunresponsive patients (4). Potassium citrate is believed to exert its beneficial effect through its citraturic and urinary alkalinizing actions. The increase in urinary citrate retards spontaneous nucleation and agglomeration of calcium oxalate crystals (5). Moreover, by increasing urinary pH and decreasing urinary content of undissociated uric acid, this treatment is useful in preventing uric acid stones (6).There are patients who are not able to tolerate potassium citrate, however, because of gastrointestinal adverse effects. Some may prefer nonpharmacologic therapy. In such cases, dietary sources of citrate may be considered an option or alternative to pharmacologic agents. Fruits and fruit juices with high citrate content generally are assumed to deliver an alkali load. However, previously published studies on the influence o...

Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing.