ABSTRACT. Background: Metabolic bone disease (MBD) is a significant complication in patients receiving long-term home parenteral nutrition (HPN). Pamidronate has been poorly studied in this population. We examine the prevalence and risk factors for MBD and examine changes in bone mineral density (BMD) after pamidronate administration. Methods: First, a chart review of patients receiving HPN for >1 year was performed, and Pearson correlations were used to assess associations between MBD (defined as t score
The incidence of metabolic bone disease (MBD) in patients receiving long-term home parenteral nutrition (HPN) is unknown. Reports from 20 years ago suggested a high prevalence of both osteoporosis and osteomalacia directly related to the administration of HPN.1-3 One recent study suggested a prevalence of MBD of 84% in patients receiving HPN.4 Other recent studies, however, suggest that perhaps MBD in patients receiving long-term HPN may primarily be a consequence of the underlying medical illness as opposed to toxicity of HPN.5

Traditional risk factors for MBD include female gender, advancing age, low body weight, glucocorticoids, excessive alcohol consumption, smoking, and physical inactivity.6 Multiple parenteral nutrition (PN) factors contribute toward MBD. These include calcium, vitamin D, and phosphate deficiencies; aluminum toxicity; acidosis; vitamin D toxicity; and amino acid infusions. Amino acid infusion increases urinary calcium excretion. Particularly, infusions exceeding 2 g/kg enhance urinary calcium loss to degrees greater than that originally infused.7 Phosphate enhances calcium reabsorption by the renal tubules.8 Adequate amounts of phosphorus must be present in PN in order to achieve a positive calcium balance. Chronic metabolic acidosis is known to impair vitamin D metabolism, leading to MBD similar to osteomalacia.9 Additionally, acidosis can lead to bone loss directly. In the early days of HPN, aluminum toxicity had a role in contributing toward MBD. Aluminum contamination resulted from contamination of amino acid solutions prepared from protein hydrolysates.10 Aluminum toxicity reduces parathyroid hormone (PTH) secretion and decreases serum levels of 1,25 dihydroxyvitamin D. In the past few years, there has been minimal contamination of amino acid with aluminum; hence, MBD resulting from aluminum toxicity should be far lower. However, there is still aluminum present in various trace elements, but in such low quantities that it is not felt to contribute to MBD to any significant degree. Vitamin D toxicity is possibly associated with MBD in patients receiving long-term HPN.2

Multiple studies have demonstrated that the risk of fractures increases with declining bone mineral density (BMD).11,12 The European Prospective Osteoporosis Study showed the risk of vertebral fracture increased by a factor of 1.5 per 0.1 g/cm^sup 2^ decrease in the BMD of the spine.13 There are no prospective trials assessing the relationship between dual energy x-ray absorptiometry (DEXA) and fracture risk in patients receiving HPN.

Nishikawa et al14 showed that IV pamidronate improved BMD in the lumbar spine after pamidronate infusion in patients receiving HPN for short bowel syndrome.

No recent Canadian study has evaluated the prevalence of MBD in patients receiving long-term HPN, nor have there been many studies evaluating the efficacy of IV pamidronate in this population. Due to the controversial issue of PN as a risk factor of MBD, we sought to examine the prevalence and risk factors for MBD in patients who are currently receiving long-term HPN in the Toronto General Hospital HPN program, and we also evaluated the change in bone density after administration of pamidronate in this patient population.

METHODS

First, a retrospective chart review of 25 patients enrolled in the HPN program for a minimum of 1 year was performed. The 25 patients studied represented all of the patients receiving HPN in our program for at least 1 year. Ethics approval was obtained from the University Health Network Research Ethics Board. All patients signed informed consent forms. Twenty patients receiving long-term HPN had BMD of the lumbar spine, femoral neck, and hip evaluated using DEXA scan. Not all patients had their DEXA performed with the same machine. Although all patients are part of the Toronto General Hospital program, some are scattered throughout the province. Hence, most of these patients’ investigations were performed closer to their home and not at Toronto General Hospital. The DEXA machines used for this study were not calibrated between centers.

Protein hydrolysate solutions were changed to free amino acid solutions with a much lower aluminum contamination in 1985. Two patients began receiving HPN before this date. One patient had been receiving HPN for 13 years, whereas the other patient started receiving HPN 6 months before 1985.

Osteopenia was defined according to the most recent WHO criteria oft score -2.5

Second, changes in BMD after administration of pamidronate were analyzed prospectively from 1998 to 2005. A subgroup of 11 patients with established osteoporosis received IV pamidronate. BMD was performed before receiving pamidronate and after 22.15 ± 5.44 months of therapy. Pamidronate was infused at home over 2 hours at a dose of 30 mg every 3 months.