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A Review of the Relationship Between Parenteral Nutrition and Metabolic Bone Disease
* University of California, San Francisco, San
Francisco, California; and Correspondence: Marcus Ferrone, University of California, San Francisco, Drug Product Services Laboratory, 3333 California Street, Suite 420, San Francisco, CA 94118. Electronic mail may be sent to ferronem{at}pharmacy.ucsf.edu. Metabolic bone disease (MBD) refers to the conditions that produce a diffuse decrease in bone density and strength because of an imbalance between bone resorption and bone formation. MBD can be a potential complication in patients receiving chronic parenteral nutrition (PN) therapy and the management of this condition presents a challenge for many clinicians. The etiology of PN-associated MBD is poorly understood, but traditional risk factors can include malnutrition, vitamin and mineral deficiencies, toxic contaminants in the PN solution, concomitant medications, and presence of certain disease states. Although additional studies are warranted to further elucidate the development and management of this condition, the following review discusses some of the important factors that may play a role in the genesis of PN-associated MBD and evaluates some potential strategies for the diagnosis and treatment of this complication. Metabolic bone disease (MBD) refers to the conditions that are characterized by a diffuse decrease in bone density and strength. This loss of bone mineral density (BMD) and ensuing osteoporosis or osteomalacia can be associated with long-term parenteral nutrition (PN) administration and is a serious and enigmatic issue for patients and clinicians alike. Although a comprehensive understanding of MBD and the compromise in skeletal architecture secondary to PN is not known, its consequences can severely affect the rehabilitation of patients and their quality of life. The true incidence of PN-associated MBD (PN-MBD) in adults remains unknown. It is estimated that 40%–100% of adult patients receiving chronic PN may have some degree of bone demineralization.1–3 The incidence and prevalence of PN-MBD in children are also unidentified; however, fractures and rickets have been associated with this clinical condition.4 Although bone disease can result in considerable infant morbidity, there is a paucity of data on the epidemiology of MBD in pediatrics.5–8
MBD is a heterogeneous complication that may result from chronic PN therapy. To gain an appreciation for this clinical condition, an understanding of fundamental bone physiology is important. The skeletal system is a dynamic organ that provides the body with mechanical stability and structural support, in addition to protecting internal organs. It produces erythrocytes and other hematopoietic elements, serves as a reservoir of calcium and other life-supporting ions, and can bind toxins and heavy metals along its enormous mineral surface, thereby minimizing their ability to cause cellular damage. Trabecular and cortical bones are the 2 major types of bone in the adult skeleton. Trabecular or cancellous bone surrounds the marrow and appears as fine, lacelike strands that make up the inner framework of the bones and gives bone its compressive strength. Trabecular bone makes up the major portion of the vertebrae, the ends of long bones, and the pelvis.9 Cortical bone is located around the circumference of the bone shaft and is made of thick, densely packed layers of mineralized collagen. It is responsible for giving bone its rigidity. All bones in the body undergo constant modification and remodeling. Remodeling or bone turnover is the process by which bone is repaired and reinforced to compensate for the mechanical stress placed on the skeleton by repetitive activity. This continuous breakdown and renewal of bone consists of the balanced activity of skeletal destruction (or bone resorption) by osteoclasts and skeletal reconstruction (or bone formation) by osteoblasts.10 On an annual basis, about 4% of cortical bone is remodeled, contrasted to approximately 28% of trabecular bone.11 The intricate process of skeletal remodeling is carefully regulated by numerous factors, including parathyroid hormone (PTH), vitamin D, and serum calcium, magnesium, and phosphorus concentrations. Any disturbance in this process over time can lead to the development of MBD.
Definitions and Clinical Presentation MBD associated with PN may present as osteomalacia, osteopenia, or osteoporosis. Osteomalacia is a disorder of mineralization of the newly formed organic matrix, leading to soft bone. In children, this abnormal calcification of the protein matrix is referred to as rickets. Osteopenia is a state of low bone mass that is due to a decrease in bone mineralization. In the progression of MBD, the bone experiences a phase of osteopenia before leading to a greater loss of BMD or the state of osteoporosis. Osteoporosis is defined by a low total bone mass and disruption of the normal architecture of bone, resulting in increased fragility and enhanced risk of fracture. Histologically, the cortices are thinned and porous. The trabeculae are few in number, thinner, and less connected. Most patients with PN-MBD will be asymptomatic; however, some will present with atraumatic bone pain and fractures. Biochemical parameters associated with bone formation and mineralization are often normal but may be subtly abnormal.12–14 These laboratory results may reveal hypercalcemia, hypocalcemia, hypercalciuria, normal 25-hydroxyvitamin D with a low 1,25-dihydroxyvitamin D level, elevated serum alkaline phosphatase levels, and low to normal PTH concentrations.
Diagnosis of MBD The best method to assess a mineralization defect in bone and establish the diagnosis of osteomalacia is by bone biopsy after double tetracycline labeling. This method is an effective tool in measuring bone growth or regression; however, it is invasive and expensive.16 Double tetracycline labeling involves a patient ingesting 2 doses of the antibiotic tetracycline at a specific interval. The tetracycline is absorbed onto the surface of existing bone structure. By spacing the doses of tetracycline, one can view deposition of a dose in the skeleton, the subsequent skeletal growth activity over time, and then the second layer of drug deposition. By measuring growth between the first and second doses, physicians can gain information as to the activity of skeletal structure within a given time frame. Histologic examination of bone tissue is necessary for diagnosis because patients may have a mixed picture of osteomalacia and osteoporosis.17,18 Osteomalacia may be present without associated clinical, radiologic, or biochemical abnormalities.17 Adults afflicted with osteomalacia have also reported more clinically apparent bone pain, especially in the periarticular areas of weight-bearing joints.12,13 Osteopenia or fractures either as an incidental radiographic finding or as reported by patient symptoms are the most common adult presentation of MBD. Osteoporosis and osteopenia are best diagnosed by direct assessment of BMD with DXA. This modality uses low-dose radiation to measure the BMD of the lumbar spine, femoral neck, and radius.19 The BMD of the individual is compared with that of a control group composed of young, gender-matched adults. Any deviation from control is expressed as standard deviations (SDs) above or below the mean and referred to as a T score, or classification of osteoporosis fracture risk. The World Health Organization has defined a T score of –1 SD or above as normal, a T score between –1 and –2.5 SDs as osteopenia, and a T score at or below –2.5 SDs as osteoporosis.20 Repeated measurements are generally performed every 1–3 years if DXA results are normal.
MBD associated with long-term PN was first described in the 1980s.12–14,21 Several PN-related factors that may increase the risk of reduced bone mass include nutrient and mineral deficiencies, excessive urinary calcium excretion, metabolic acidosis, high aluminum concentrations in PN, medications, and underlying medical conditions.
Deficiencies in Calcium and Phosphorus Adequate supplementation of calcium and phosphorus in PN solutions has been a continual problem. The risk of calcium-phosphate precipitation in solution limits the amounts of these electrolytes that can be provided in PN. This is particularly prevalent in solutions for neonates because their calcium and phosphorus needs are high, yet fluid requirements are restricted.24,25 Factors that can enhance precipitation in PN admixtures include high calcium and phosphorus concentrations, decreased amino acid concentration, increased environmental temperature, elevated pH and prolonged hang time of the PN solution.26–28 Calcium-phosphate solubility curves (Figure 1) are routinely used to identify potential solubility complications in PN. A clinical pharmacist trained in the compounding of PN solutions and interpreting these graphs can assist the clinician in maximizing the calcium and phosphorus concentrations for a prescribed regimen.
Excessive Urinary Calcium Excretion Excessive dietary protein is known to enhance urinary calcium excretion and may lead to a negative calcium balance.30 The precise mechanism for this effect is unknown; however, calcium resorption by the renal tubules has been shown to decrease in response to a protein meal. Part of this effect may be related to sulfate excretion and insulin release, both of which occur with protein metabolism and are known to decrease renal calcium resorption. Studies have revealed a dose-dependent correlation between the amounts of amino acids in PN and urinary calcium excretion. Bengoa et al31 infused a PN formula into infants with 1 g/kg/d of amino acids vs 2 g/kg/d and demonstrated a modest increase in urinary calcium from 287 ± 46 mg/d to 455 ± 58 mg/d. Concentrations of calcium, PTH, and 25-hydroxyvitamin D were normal and unchanged during the 3 weeks of study. The investigators suggested that the increase in hypercalciuria was partially due to an increase in glomerular filtration rate and perhaps a decrease in reabsorption. It is likely that increased levels of sulfate, titratable acid, and insulin all played a role in this observed increase. Other investigations have confirmed the correlation between amino acid intake and calciuria.32 It is also postulated that the infusion of intravenous (IV) amino acids causes an increased glomerular filtration rate or increased urinary acidity, which in turn decreases renal calcium resorption. The provision of amino acids with their low pH contributes significantly to the acidity of the PN solution. A high-protein load in PN formulas may play a role in hypercalciuria through mobilization of calcium carbonate stored in bone as a buffer for the acidic load generated in the metabolism of sulfur-containing and neutral amino acids. However, it is unknown whether the effects of amino acids on increasing urinary calcium excretion are related to their pH-lowering capacity or through other unidentified mechanisms.1,33
Metabolic Acidosis and Calcium Deficiency Lactic acidosis resulting from disordered gastrointestinal flora has also been linked to the development of osteomalacia and bone fractures in patients with SBS. Some patients receiving home PN may develop bacterial overgrowth syndrome, where the bacteria can produce D-lactate, a form of lactate that is not cleared from the body as readily as the normal L-lactate. Karton et al34 observed that patients with SBS receiving long-term PN had significant levels of serum and urine D-lactate. Evidence of decreased rate of bone formation and osteomalacia was revealed in the bone biopsies of these patients. It is unclear from this report whether chronic D-lactic acidosis will lead directly to bone loss; however, the report suggests that this may be a factor in some individuals.
Cyclic PN and Hypercalciuria
Aluminum Contamination Reports describing aluminum toxicity related to PN surfaced in the early 1980s when casein hydrolysate was used as a protein source. These particular solutions resulted in the infusion of 3400 µg/d of aluminum compared with 33 µg/d in solutions made with crystalline amino acids.36 Several studies in which patients received casein hydrolysates showed significant detectable amounts of aluminum in plasma, urine, and bone, compared with findings in patients receiving crystalline amino acid solutions. Adults receiving 2–3 mg of aluminum per day from casein hydrolysate PN solutions developed symptoms of bone pain within 2–36 months after initiation of PN.13,39 Reduced trabecular bone area and rate of bone formation were shown in iliac crest bone biopsies, along with an increased amount of stainable aluminum on bone biopsy and high plasma and urinary aluminum concentrations in patients exposed to casein hydrolysate solutions.39–44 Discontinuation of PN resulted in reduction of bone pain and hypercalciuria, improvement in bone formation rate, and return of serum concentrations of 1,25-dihydroxyvitamin D to normal. According to the above findings, some investigators have speculated that circulating aluminum reduces bone formation even before it accumulates in bone. Casein hydrolysate was withdrawn from the market in 1981 after these studies proved the formulation contained an unfavorable amount of aluminum. By changing from casein hydrolysates to crystalline amino acid solutions, patients receiving long-term PN showed a 50% reduction in plasma and urinary excretion aluminum levels.42,45 Phosphate salts, calcium salts, ascorbic acid, and heparin are now the primary offenders for aluminum contamination. Other additives used in PN solutions, including multivitamin and trace element preparations, amino acids, and magnesium salts, also contain various amounts of aluminum. In 1990, concerns were raised regarding the aluminum content in these parenteral products. By January 2000, an US Food and Drug Administration (FDA) rule was proposed to require manufacturers to limit the concentration of aluminum in large-volume parenterals (LVPs), small-volume parenterals (SVPs) and pharmacy bulk packages (PBPs) to no more than 25 µg/L.46 The rule mandates that this maximum amount of aluminum at expiry be stated on the immediate container label for SVPs and PBPs. After an amendment in 2003 that allowed manufacturers to state "contains no more than 25 µg/L" on a label instead of listing the exact aluminum content, the rule became effective in July 2004. The final rule also states that labeling of LVPs, SVPs, and PBPs used for the compounding of PN must include a statement on aluminum contamination, particularly for patients with renal insufficiency or prematurity. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) does not have any specific standards regarding aluminum content in PN admixtures and considers the rule to apply to manufacturers and not pharmacists.46,47 The prevalence of PN-MBD secondary to aluminum toxicity is now considerably lower given that current PN solutions contain far less aluminum concentrations compared to admixtures prepared 2 decades ago. This has been corroborated by a report of the metabolic abnormalities associated with PN-MBD that did not find the marked hypercalciuria, hypercalcemia, and low 1,25-dihydroxyvitamin D levels previously attributable to aluminum.21 However, this cause should not be dismissed when encountering chronic PN patients who develop MBD and present with concomitant renal insufficiency or immature renal function.
Vitamin D Requirements Bone loss associated with vitamin D deficiency has long been recognized. Vitamin D deficiency results in osteomalacia in adults and rickets in children.18 Patients with chronic renal failure, liver failure, or malabsorption syndromes are at increased risk for vitamin D deficiency. Although this has little importance in the patient who receives IV vitamin D, patients may have developed vitamin D deficiency before initiation of PN. For example, vitamin D deficiency is not uncommon in patients with Crohn's disease and is usually related to steatorrhea associated with deficient bile salt reabsorption.50 Relatively brief sunlight exposure, in the absence of sunscreen use, will provide most if not all of the daily vitamin D requirements.50 Some home PN patients avoid outdoor activities; therefore, their sole source for vitamin D may be PN. In patients receiving chronic PN, the possibility of vitamin D toxicity causing MBD has been raised. The dose of vitamin D usually added to adult PN formulas is 200 IU/d. Dosages for children are higher and range from 260 IU/d to 400 IU/d, depending on the body weight of the patient. Anecdotal reports of withdrawal of vitamin D from PN suggest improvement in the signs and symptoms of MBD. In these studies, the short-term withdrawal of vitamin D led to corrections of hypercalcemia, hypercalciuria, and osteomalacia. Improvement in bone disease following withdrawal of vitamin D was first observed by Shike et al.12 Shike and colleagues51 further examined the effect of removing vitamin D for 6 months from PN solutions in 11 patients. Patients experienced relief of MBD symptoms, including hypercalcemia, hypercalciuria, bone fractures, and pain, as well as a significant reduction in osteoid index, with increased bone mineralization on bone biopsy. However, these patients may have had secondary hyperparathyroidism before starting PN in which bone metabolism was already impaired. It is also possible that relatively high concentrations of 1,25-dihydroxyvitamin D resulted in an increase in bone resorption.52 In another investigation where vitamin D was withdrawn for an average of 4.5 years, Verhage et al53 demonstrated improvement in bone mineral content of the lumbar spine and normalization of blood PTH and 1,25-dihydroxyvitamin D. Serum levels of calcium, phosphorus, magnesium, and 25-hydroxyvitamin D were found to be in the normal range at the start of the study and remained so during the time that vitamin D was withheld. Larchet and colleagues54 explored the effects of discontinuing vitamin D in children receiving PN. This resulted in a marked decrease in serum 25-hydroxyvitamin D concentrations into the vitamin D–deficient range, but serum concentrations of 1,25-hydroxyvitamin D, calcium, and phosphorus remained normal. There were no consistent changes in urine calcium and phosphorus excretion, and no apparent clinical effects were detected up to 2 years. In summary, the vitamin D requirement is minimal for patients requiring PN and does not seem to be greater than the recommended dose for patients receiving a normal diet. Because it is well known that chronic vitamin D deficiency can result in bone disease, it would seem prudent to maintain normal vitamin D status in patients receiving PN. This practice complements the general goal of maximizing the absorption and retention of any enteral nutrients tolerated by these patients because the vitamin D metabolite promotes the intestinal absorption of calcium and phosphorus. In addition, it is not possible to remove vitamin D from a PN solution and still provide appropriate amounts of the remaining 12 vitamins. Thus, until further evidence becomes available, complete discontinuation of vitamin D supplementation for patients requiring PN is not recommended.
Vitamin K Deficiency A deficiency in vitamin K may develop secondary to alteration of the colonic microflora from broad-spectrum antibiotic use, or may be associated with fat malabsorption. This reduction of vitamin K can result in an undercarboxylation of the vitamin K-dependent proteins involved in bone metabolism and lead to decreased bone mineralization.59 An investigation by Hodges et al60 examined elderly women with osteoporotic fractures and found lower serum vitamin K concentrations compared with levels in control subjects. Serum concentrations of undercarboxylated osteocalcin were inversely correlated with BMD and positively correlated with hip fractures. In another study, osteoporotic patients treated with vitamin K showed a decrease in bone loss and an increased concentration of bone formation markers.61 Recent work by Schoon et al62 revealed an inverse relationship between serum concentrations of undercarboxylated osteocalcin and BMD of the lumbar spine in 32 patients with longstanding Crohn's disease. Because the actual effects of vitamin K on bone mineralization and formation remain unclear, further studies are warranted.
Fluoride Exposure A recent retrospective analysis of patients with SBS receiving home PN was conducted to ascertain the relationship between fluoride status with bone condition.65 This study revealed a strong positive correlation between serum fluoride concentrations and lumbar BMD but no correlation with femoral neck BMD. The investigators reported that femoral neck BMD at baseline and throughout the study was significantly lower than spine BMD. In fact, femoral BMD remained stable, whereas spinal BMD showed an overall increase. Although these results differ from those of Haderslev et al,66 who reported lower BMD over the duration of PN at both the femoral and the spinal sites, these discrepancies could be related to the high fluoride concentrations found in the patients of this current study.65 The high intakes of fluoride are frequent in this patient population because of beverages ingested to compensate for stool and stoma losses. Therefore, the increase in BMD at lumbar sites in patients with SBS and PN-MBD could be related to high serum fluoride concentrations and the action of this electrolyte on trabecular bone formation, which increases cancellous bone density. This hypothesis is in agreement with the correlation observed between serum fluoride levels and the osteocalcin concentration, which is considered to be a sensitive and specific marker of osteoblastic activity. On the other hand, fluoride concentrations play no role in femoral BMD, because fluoride is known to have no effect on cortical bone density.64
Concurrent Medications Long-term heparin therapy (both standard and low-molecular-weight moieties) has been associated with decreased bone density and vertebral fractures.72,73 Unfortunately, the effects of heparin line flushes and addition of low-dose heparin to PN solutions have not been evaluated. Much of the information concerning the adverse effects of heparin on bone comes from studies of pregnant women requiring therapeutic anticoagulation. Some home PN patients may receive warfarin as prophylactic therapy against catheter thrombosis or to treat a previously diagnosed thrombosis. The long-term use of this medication has been associated with a reduction in BMD, especially in rapidly growing bone as present in children, although this has not been demonstrated in all studies.74–76
Concomitant Disease States A common digestive disorder for which patients require PN is IBD. These patients are predisposed to develop MBD if they are malnourished, malabsorb nutrients such as calcium and vitamin D, or receive corticosteroids to control their disease. A large population-based cohort study of 6027 patients with IBD matched to healthy control subjects showed a 40% increased rate of fractures in this patient population.78 The fracture rate was the same in patients with Crohn's disease and those with ulcerative colitis (UC). The inflammatory process of the disease state itself has been suggested to play a role in the development of MBD. Cytokines are elevated in patients with active disease and these molecules stimulate osteoclast activity resulting in low BMD.79–81 Many studies hypothesize that low BMD is often associated with the use of corticosteroids. Bishchoff et al82 reported that the prevalence of osteopenia and bone fracture was significantly correlated with cumulative corticosteroid dose and number of active phases of IBD. Abitbol and colleagues83 evaluated 84 patients with IBD, including 34 with Crohn's disease and 50 with UC. BMD by DXA showed osteopenia in 43% of patients, 52% of whom were receiving glucocorticoid treatment. Seven percent had vertebral fractures. A significant correlation between age, cumulative corticosteroid dose, low osteocalcin levels, and BMD of the spine was demonstrated. Haugeberg et al84 documented a 6%–8% reduction of BMD in patients with Crohn's disease compared with control subjects, and the use of corticosteroids was the only disease-related factor associated with low BMD. Another population-based study of patients with IBD matched with control subjects for sex and age showed reduced BMD in Crohn's disease vs UC.85 Disease extent, duration, and location did not influence the rate of low BMD in the 2 patient groups. However, corticosteroid use was significantly associated with low BMD in Crohn's disease but not in UC. Women with chronic illnesses such as IBD may develop amenorrhea. Similarly, in the absence of supplementation, postmenopausal women who require home PN will also develop estrogen deficiency. This deficiency in estrogen appears to place women with Crohn's disease or severe malnutrition at a greater risk for the development of bone disease.86,87 Androgen deficiency is also associated with osteopenia in both men and women, probably because of defective osteoblast activity and reduced bone formation.88,89 Severe intestinal malabsorption can also increase the risk of bone abnormalities. Most calcium enters the body through the ingestion of lactose-containing products. Patients that require PN because of malabsorption secondary to SBS can therefore develop calcium deficiencies. Calcium malabsorption is often linked with steatorrhea, so patients with Crohn's disease or celiac sprue may even have preexisting calcium deficits.90 It is also possible that this deficit may have originated from lactose maldigestion prior to the initiation of PN.91 This deficiency can lead to a negative calcium balance and ultimately have a profound effect on skeletal health. Paradoxically, the effects of underlying illnesses and associated nutrition deficiencies may become more prominent with improvement of the general nutrition status of the patient.4,41,92 For example, in infants, nutritional rickets tends to develop during the period of postnatal "catch-up" growth during recovery from serious illness.5,23 A similar observation is noted in adult patients where symptomatic bone disease can often occur after significant weight gain; however, the pain improves following discontinuation of the PN.13
Patients receiving chronic PN should be routinely assessed and monitored for MBD. Clinicians can monitor for physical signs of MBD by checking for a loss of height or reports of bone or back pain from their patients. DXA measurements can be obtained at baseline and repeated every 2–5 years in stable patients and every 12–18 months in individuals with newly diagnosed condition or those receiving pharmacotherapy affecting bone metabolism. If T scores are less than –1, the patient should be considered for referral to an endocrinologist for further evaluation and treatment. Quarterly to semiannual tests for serum levels of vitamin D and PTH may help to determine the need for modification of nutrient intake. In addition to these common clinical practices, the discussion below highlights supplemental details to assist in the management and therapy of PN-MBD.
Calcium and Phosphorus Intake For adult patients, supplying at least 15 mEq calcium and 15 mmol phosphorus on a daily basis can promote retention of these elements. Sloan et al95 showed that these doses of calcium and phosphorus are needed in patients who are receiving continuous PN infusion. The participants of this study received weekly doses of vitamin D and nearly all of the patients had an underlying malignancy. Although the doses of calcium and phosphorus administered in this investigation may not be directly applicable to patients receiving long-term PN, it highlights the importance of providing an adequate amount of substrate for normal calcium metabolism. Wood et al35 showed that a positive calcium balance could be achieved when greater amounts of phosphorus are provided in a PN formula. Phosphorus appears to enhance calcium reabsorption by the renal tubules and this is independent of PTH, plasma calcium, and renal sodium handling. It should be noted that while high doses of phosphorus have been shown to reduce calciuria, chronic excess of this electrolyte can lead to bone loss as a result of secondary hyperparathyroidism.
Other PN Regimen Adjustments
Pharmacologic Treatment Antiresorptive agents inhibit the action of osteoclasts, preserve bone structure, prevent further bone loss, and improve bone strength. Bisphosphonates are the most commonly used drugs for the treatment of osteoporosis and have proven effective in reducing fracture risk in women and men, as well as in patients with osteoporosis due to corticosteroid therapy. Bisphosphonates modify calcium metabolism and reduce bone marrow differentiation and the recruitment of osteoclast precursors, and also induce apoptosis of osteoclasts.96,97 These mechanisms result in a decreased number of osteoclasts and less bone resorption. The reduction in the risk of fracture during antiresorptive treatment is related to the magnitude of change in BMD and remodeling activity.98 Bisphosphonates are generally administered orally and are poorly absorbed from the intestines, which can be of particular concern in patients requiring PN due to intestinal failure and malabsorption. Gastrointestinal discomfort is also the most common side effect. Some bisphosphonates are available in IV form, which may provide a therapeutic option for patients with significant intestinal failure. Haderslev et al99 were the first to explore the benefits of an IV bisphosphonate in a group of patients receiving long-term PN who had evidence of abnormal BMD. In a prospective, randomized, double-blind, controlled trial, the effects of IV clodronate, a bisphosphonate available in Europe, were compared with placebo. Biochemical markers of bone resorption were statistically lower in the bisphosphonate group, and a significant increase in BMD in the forearm was reported. Although BMD was also increased in the spine and hip, this result was not statistically significant. Nishikawa and colleagues100 demonstrated in 10 of 11 home PN patients with SBS that lumbar sacral DXA results improved while receiving IV pamidronate for decreased BMD. In another recent prospective trial that examined patients with a more diverse set of indications for home PN, Raman et al101 showed that BMD results had trends toward improvement via the mean T score of the spine and hip after IV pamidronate therapy. Although the results of the above research suggest promise for IV bisphosphonates, larger sample sizes are needed to evaluate the true efficacy of this medication. The recombinant PTH teriparatide (Forteo; Eli Lilly, Indianapolis, IN) is a subcutaneously administered anabolic agent approved by the FDA in 2002 for the treatment of osteoporosis in postmenopausal women at high risk for fractures. A recent clinical observation has been reported in the literature, describing the use of teriparatide in a patient with significantly low bone mass and receiving PN secondary to intestinal resection after radiation therapy.102 This case study reports normalization of BMD after 18 months of treatment in a patient with established osteoporosis. Although the causes of low BMD in this case are likely to be multifactorial and the increase in BMD by 2.5 SDs after treatment should be examined with caution, the case establishes an initial foundation on which our knowledge on the effects of bone anabolic agents can grow. Prospective studies are still needed to establish the use of intermittent PTH administration in patients requiring PN to prevent skeletal complications.
The pathogenesis of PN-MBD is poorly understood and likely multifactorial. Patients receiving chronic PN often had debilitating primary disease and malnutrition that predispose them to derangements in bone metabolism. The role that toxic contaminants in artificial nutrition once played in this pathology has been markedly reduced over the past 2 decades; however, nutrient deficiencies and concurrent medications may still play a viable role in the origin of this bone disorder. Clinicians must remain vigilant when treating patients receiving chronic PN in order to provide them with a more healthy future. Additional investigations are also warranted in order to determine the utility of interventions designed to maintain and promote skeletal health.
Nutrition in Clinical Practice, Vol. 22, No. 3,
329-339 (2007) This article has been cited by other articles:
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Bone Physiology
Clinical Presentation and...
