One of the most prevalent of the degenerative diseases in the United States today, osteoporosis affects over 10 million individuals. An additional 18 million are at risk of osteoporosis due to low bone density. The majority of patients affected are postmenopausal females. The number of cases of osteoporosis is expected to rise substantially in the next several decades, as life expectancy increases and the world population expands. This growing elderly population inevitably will be affected by multiple pathological processes that require drug therapy. Unfortunately, some medications may cause hypocalcemia and accelerate bone loss. Patients who experience these effects can present with osteoporosis, osteopenia, and/or osteomalacia.
Osteoporosis, Osteopenia, Osteomalacia
Defined as a reduction in bone mineral mass and an increase in the porosity of remaining bone cortices and trabeculae, osteoporosis is associated with bone thinning. In addition, there is a resultant decrease in bone strength and increased susceptibility to skeletal fracture — even with minimal trauma. Osteopenia is the loss of bone density, as seen on radiographic exam. The reduced density may occur in all bones or be limited to a specific bone, as in the case of disuse atrophy. Osteomalacia and rickets are disorders that involve the softening of bone due to a failure of osteoid matrix cells to mineralize properly. This failure to mineralize occurs as a result of vitamin D deficiency and inadequate intestinal absorption of calcium and phosphorus.
While none of the above disorders is involved in development of bone disease, all are associated with an alteration in normal bone development. Although in osteoporosis there is typically a net excess of bone resorption in relation to bone formation, the exact amount may vary from patient to patient. Numerous factors may increase the risk of developing bone disease, including the use of certain medications. Table 1 provides a list of medications associated with inducing bone disease.
| Table 1: Agents Associated with Inducing Bone Disease |
|
| Acetazolamide Aldesleukin Alendronate Alprostadil Aluminum Amifostine Amikacin Amphotericin B Amphotericin B liposome Basiliximab Bleomycin Busulfan Bumetanide Capreomycin Carboplatin Cholestyramine Cisplatin Citrate liposome Citrate salts Clodronate Codeine Colestipol Corticotropin Coumadin Daunorubicin Didanosine Diethylstilbestrol Doxorubicin hydrochloride liposome Edetate disodium Epinphrine Ethacrynic acid Etidronate disodium Fluocortolone Fluoride salts Fluorouracil Foscarnet Furosemide |
Gallium nitrate Gentamicin Glucocorticoids Glutethimide Growth hormone Heparin Ibandronate Interferon alfa-N1 Interferon beta-1B Interferon gamma Isoniazid Leucovorin Lithium Magnesium Mineral oil Mithramycin Morniflumate Neomycin Netilmicin Niflumic acid Pamidronate Pentamidine Phenobarbital Phenytoin Phosphates Polymyxin B Retinoic acid Sargramostim Sodium polystyrene sulfonate Tamoxifen Teceleukin Terbutaline Teriparatide Tobramycin Torsemide Triamterene Warfarin Zolendronate |
Agents Needed for Bone Maintenance
The primary agents responsible for bone remodeling and mineral metabolism are parathyroid hormone (PTH), vitamin D, and calcitonin.
Role of PTH: Parathyroid hormone stimulates bone resorption by stimulating increased reabsorption of calcium and decreased phosphorus reabsorption in the kidney. PTH also increases the renal production of 1,25-dihydroxy D3 (calcitriol), thus increasing the intestinal absorption of calcium and phosphorus. This ultimately leads to bone mineralization and resorption. The outcome is a net increase in ionized serum calcium levels.
Role of Vitamin D: Vitamin D is necessary for proper bone maintenance. It can be ingested from dietary sources such as fatty fish or from fortified foods such as milk, bread products, cereals and margarine. Alternatively, it can be synthesized endogenously in the skin during sun exposure. Regardless of its source of origin, vitamin D must be hydroxylated in the liver to its major circulating form — 25(OH)D3. Twenty-five (OH)D3 is biologically inert on calcium metabolism at physiological concentrations; it requires further hydroxylation in the kidney to its biologically active metabolite, 1,25(OH)2D3 (calcitriol).
The active form of vitamin D primarily maintains serum calcium levels within normal range. It accomplishes this by enhancing the efficiency of intestinal calcium absorption and/or mobilizing calcium stores from bone. Any medication that interferes with the metabolic conversion of vitamin D to its active form will impair calcium absorption and alter bone status. For example, even the topical application of sunscreen products containing para-amino benzoic acid (PABA), with a protection factor of 8, can almost completely eliminate the in vivo cutaneous synthesis of vitamin D and predispose chronic users to osteoporosis.Table 2 provides a list of medications and respective mechanisms involved in precipitating bone disease.