After entering systemic circulation, drugs can distribute into the interstitial fluid and the intracellular fluid of various tissue cells. As drugs bind to different cellular components, their accumulation may occur in various tissues. Drugs bound to tissue components serve as reservoirs that slowly release the free drug, prolonging drug action. However, drug accumulation may cause local toxicity. For example, acrolein, the metabolic product of cyclophosphamide, binds to renal tissues and accumulates in renal cells, exerting its nephrotoxic effects. Lipophilic drugs bind to body fat, and since fat is a poorly perfused tissue, it serves as a stable drug reservoir for such drugs. Bones may also function as drug storage sites. An example is treating osteoporosis using alendronate therapy. The phosphonate binds to hydroxyapatite crystals in the mineralized bone matrix and resists degradation, preserving the bone matrix. Bones may also function as a reservoir for toxic metals. The slow release of toxins into the blood can give rise to a range of adverse effects.