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|Newsletters: Update on Metabolic Bone Disease in Long-Term HPN Consumers|
Update on Metabolic Bone Disease in Long-Term HPN Consumers: Evaluation, Prevention, Treatment
Douglas L. Seidner, M.D., Co-Director, Nutrition Support Team, Cleveland Clinic Foundation
In the May/June 1999 LifelineLetter, the topic of metabolic bone disease (MBD) in long-term home parenteral nutrition (HPN) consumers was thoroughly reviewed. The article pointed out that bone remodeling, the process of breaking down old bone and making new bone, is a normal process, and the gradual loss of bone is also part of the aging process. However, in some HPN consumers the normal process of bone remodeling is defective and the consumer is at risk for developing MBD. HPN consumers are at risk for osteoporosis or osteomalacia (two forms of MBD seen with HPN) first, because of their underlying illness or the medications used to treat their disease; and second, because HPN, especially during the initiation of therapy, may promote urinary calcium loss and bone demineralization.
Since MBD can develop with few, if any symptoms, and since it can result in fragility and atraumatic bone fractures in the future, it is important for consumers to take an active role in their care to make certain appropriate measures are taken to identify the presence of MBD; their HPN is optimally prepared to maintain calcium balance; and when appropriate, adjunctive therapy is begun to slow bone loss. This article will outline how a consumer’s medical team can evaluate and monitor a consumer for MBD, and suggest measures which can be taken to minimize the bone loss while receiving HPN.
Until recently, bone mineral density could only be measured by bone biopsy. The bone is generally taken from the hip with a fine needle. Bone biopsy is the only test which can definitively distinguish osteoporosis (bone appears structurally normal but total bone mass is depleted), from osteomalacia (bone is inadequately calcified, resulting in a prominent protein matrix and abnormal regions of bone mineralization). Bone biopsy can also show reversal of osteomalacia when therapy is prescribed. The need for bone biopsy in HPN clinical practice is infrequent since osteomalacia is uncommon and many of the measures taken to prescribe an appropriate HPN formula will manage this condition if it is present.
A variety of radiographic techniques have been developed to measure bone mass. These include computerized tomography (CT), ultrasound, single photon absorptiometry and dual energy absorptiometry (DEXA). The most commonly used method is DEXA because it can be done rapidly (usually less than 20 minutes), and the level of radiation is low (less than a single chest x-ray). I suggest a DEXA scan be performed soon after HPN is begun, especially if the consumer has a long standing condition associated with malabsorption (such as Crohn’s disease or radiation enteritis) or a risk factor for osteoporosis (such as menopause or surgical resection of the ovaries, hyperparathyroidism, hyperthyroidism, or a family history of osteoporosis). All of these conditions are risk factors for the development of osteoporosis, which means the consumer’s insurance company should pay for the DEXA. If the consumer doesn’t have any of the above risk factors, simply being on long-term HPN is an argument for a baseline DEXA scan, since long-term HPN is know to cause MBD in some cases. I suggest consumers talk to their physicians about getting this exam.
Since the metabolism of bone is slow, a DEXA scan does not need to be repeated often. A repeat scan in one year is sufficient for most people. If the consumer’s bones are normal on two measurements then he or she may be able to go two to three years between measurements. On the other hand, if the consumer’s bones are thin, the scan should probably be repeated every year. To date, guidelines have not been established for patients on HPN, but consumers should review this program with their physician.
Parenteral Nutrition Preparation
Many of the components of HPN solution may enhance calcium loss in the urine, which can lead to the development or worsening of MBD. These factors were discussed in the May/June issue of this newsletter. It should be pointed out that many of these studies involved a limited number of patients who were receiving HPN in the hospital, and may not truly reflect what happens in long-term consumers.
In a sophisticated study using Macaque monkeys as a model, it was shown that when HPN is first begun there is an increase in the amount of calcium in the urine and calcium balance is negative; however, within a short time, calcium balance returns to normal. The investigators found that the level of parathyroid hormone (PTH) gradually increased as the animals stayed on HPN. It should also be pointed out that PTH remained within the normal range throughout the study. PTH is made by the parathyroid glands located in the neck and is involved in regulating calcium and bone remodeling. I find these results reassuring because they imply one can provide HPN without being unduly concerned about the development of MBD.
First and foremost an HPN solution should contain a sufficient amount of calcium for the consumer to remain in calcium balance. Most HPN consumers require 15 mEq of calcium gluconate each day. Consumers with severe diarrhea may require more. Bones require two other minerals to maintain normal metabolism: phosphate and magnesium. These minerals should be provided in a sufficient amount to maintain normal levels in the consumer’s blood. The usual dose for phosphate is 30 to 40 mEq per day. Some investigators have suggested 15 mEq for every 1000 kcal of dextrose. The usual dose of magnesium is 15 mEq per day. It is important to note that both minerals are excreted by the kidney; thus, if the consumer has renal disease (even mild), or tends to be dehydrated, his or her requirement for these minerals may be lower. Blood levels should be maintained in the normal range.
Vitamin D is also involved in bone metabolism. A multiple vitamin additive will provide 200 IU per day and this should be enough. In fact, preparations many years ago had more than this and it was discovered that higher doses (in the range of 400 to 1000 IU per day) actually contributed to the development of osteomalacia.
HPN solutions need an adequate amount of acetate to maintain normal acid-base balance. Without it, acidosis can develop and lead to an increase in the loss of calcium in the urine. Conditions which often require extra acetate are severe diarrhea and renal disease. To monitor acid-base balance, serum bicarbonate is measured in the blood on a standard chemistry panel. The blood level consumers need to maintain depends on their medical condition; however, the level should be between 24 and 32 mEq per liter, the normal range for most labs.
Monitoring While on Parenteral Nutrition
Blood chemistry values should be measured and levels of calcium, phosphorus, magnesium, and bicarbonate kept as close to normal as possible. Depending on the result of the DEXA or blood levels of these minerals, the physician may wish to measure the consumer’s PTH and 25 hydroxy vitamin D. A twenty-four hour urine should be collected to determine calcium balance. A normal amount of calcium in the urine is 100 to 300 mg per day. If this value is low, it suggests that the consumer is not receiving enough calcium. The value can also be used to determine a calcium balance by calculating the calcium received in HPN and comparing it to the amount of calcium in the urine. These values should be close to equal. However, this is not the true balance since there may be some calcium absorbed from the diet and losses in the stool.
Medications for Metabolic Bone Disease
Medications for osteoporosis act by either promoting mineralization of the protein matrix of bone or decreasing the rate of mineral loss. Medications which are commonly used at this time are all directed toward the second mechanism. Estrogen replacement therapy (ERT) should be considered in all women who are perimenopausal or who have had surgical removal of both ovaries. ERT is contraindicated in women with a history of breast and endometrial cancer, thrombo-embolic disease and acute liver failure.
Calcitonin is a naturally occurring protein which counteracts the calcium mobilizing effect of PTH. Until recently this medication had to be given by injection since it breaks down when taken by mouth. Now it is available in a nasal spray which is taken once each day. This medication is quite safe to take.
Bisphosphonates are a class of medications which bind to the surface of the bone and inhibit the activity of osteoclasts, the cells responsible for breaking down bone mineral. Early forms of this medication are not readily absorbed and can cause ulceration of the gastrointestinal tract. More recent preparations are available for intravenous use and only need to be given every three months. The bisphosphonates are the most potent medications available to retard bone mineral loss. Bisphosphonates have been extensively studied in patients with osteoporosis, but there is little literature on their effect in HPN consumers.
Certain medications should be avoided whenever possible as they may worsen MBD. For example, corticosteroids such as prednisone are known to inhibit calcium absorption and bone mineralization, and to increase bone mineral loss. While this medication is important in the management of Crohn’s disease, attempts should be made to get on the lowest possible dose to control symptoms. This medication should never be stopped suddenly, or without conferring with your doctor. HPN consumers concerned about MBD should also avoid Lasix, a diuretic which is know to promote calcium loss in the urine. Alternatives are available which manage hypertension and excess fluid, but do not promote urinary calcium loss. Other medications which effect calcium and vitamin D metabolism include thyroid hormone (Synthroid), when given in excessive amounts, and dilantin. Tobacco and excessive alcohol use can also adversely effect bone metabolism; thus smoking cessation is important to maintain normal bone health and alcohol intake should be kept to a minimum.
Metabolic bone disease is a potential complication of HPN and gastrointestinal diseases associated with malabsorption. Non-invasive diagnostic studies are now readily available to detect the presence of MBD and to monitor treatment. HPN should be prescribed in such a way as to maintain normal calcium balance. In addition, medications such as estrogens, calcitonin and bisphosphonates, should be considered under certain circumstances to prevent the development of osteoporosis, or if it is present, to slow its progression. Finally, consumers are advised to minimize their intake of alcohol and to quit smoking to maintain bone health.
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