Medline ® Abstracts for References 5-16

Muscle cramps are involuntary, painful, sudden contractions of the skeletal muscles. They are present in normal subjects under certain conditions (during a strong voluntary contraction, sleep, sports, pregnancy) and in several pathologies such as myopathies, neuropathies, motoneuron diseases, metabolic disorders, hydroelectrolyte imbalances or endocrine pathologies. There has been considerable uncertainty in the literature regarding the classification and nomenclature of muscle cramps, both because the term "cramp" is used to indicate a variety of clinical features of muscles, leading to its use as an imprecise "umbrella" term that includes stiffness, contractures and local pain, and because the spectrum of the diseases in which it appears is wide. The purpose of the present study is to propose a simple classification to provide a framework to better recognize the full spectrum of phenomenology of muscle cramps.

Muscle cramps are involuntary, painful, spasmodic contractions of the skeletal muscle. Although cramps are a common clinical complaint, their etiology and management have not been well established. Exercise-associated muscle cramps occur during or immediately following exercise, and they are associated with muscular fatigue and shortened muscle contraction. The main challenges for treating physicians are to identify whether the complaint represents a true muscle cramp as well as to rule out the presence of an underlying serious clinical condition. Muscle cramps may be a symptom of any of several conditions, including radiculopathies, Parkinson's disease, hypothyroidism, diabetes mellitus, vascular problems, electrolyte disorders, and metabolic myopathies. Cramps also may occur as a side effect of certain drugs (eg, lipid-lowering agents, antihypertensives, beta-agonists, insulin, oral contraceptives, alcohol). Most athletes who experience exercise-associated muscle cramps are healthy individuals without systemic illness. Therapy should focus on preventing premature fatigue by means of appropriate nutrition and adequate training.

Painful involuntary skeletal muscle contractions, or cramps, are common patient complaints and may be classified as examples of true cramp, tetany, contracture, or dystonia. The pathophysiologic and clinical features of each of these diagnoses are described. The approach to the patient with cramps should emphasize the history, physical examination, and, if the diagnosis is unclear, minimal routine laboratory data. Although many therapies have been proposed for ordinary cramps, the best evidence supports stretching exercises and quinine. Areas for future study of this common symptom are proposed.

Selective estrogen receptor modulators (SERMs) are a diverse group of non-steroidal (non hormonal) compounds developed to offer the postmenopausal women many of the advantages of estrogen therapy (ET) while avoiding undesired effects on reproductive and other tissues. Tamoxifen and toremifene, first generation SERMs are used for the adjuvant treatment of breast cancer worldwide, but their stimulatory effect on the uterus prevents their widespread use in other indications. A second generation SERM, raloxifene hydrochloride, a benzothiophene SERM is fully safe for the uterus and significantly reduces the risk of vertebral fractures in postmenopausal women with osteoporosis. The safety and efficacy of raloxifene in postmenopausal women have been studied extensively in more than 40,000 women over 50 clinical trials in 30 countries. The majority of the trials have been large double-blind placebo-controlled trials, including Asia and Japan. Raloxifene is well tolerated, with the only common side effects significantly higher than placebo being hot flushes and minor leg cramps. Venous thromboembolism was the only adverse events of clinical significance but rare associated with raloxifene in Caucasian women, but was not observed so far in Asian countries.

BACKGROUND/AIMS: To determine the prevalence of muscle cramps in patients with liver cirrhosis and to identify factors associated with their development, especially serum zinc.

METHOD: One hundred cirrhotic patients and 85 healthy subjects were enrolled into the study. True muscle cramp was defined as at least 1 painful leg cramp either occurring at rest or strong enough to waken a patient from sleep, occurring at least once a week persisting for a period of greater than 1 year. Creatinine, calcium, magnesium, sodium, potassium, zinc, glucose, alanine aminotransferase, total bilirubin, and albumin levels were detected in sera. Prothrombine time was measured in cirrhotic patients. Presence or absence of ascite was determined by sonography.

RESULTS: True muscle cramps were significantly more common in patients with cirrhosis when compared with the control group (59% vs. 7.1%, respectively, P<0.001). Cramp (+) cirrhotic patients had older age (49.54 +/- 10.09 vs. 55.54 +/- 7.90, respectively; p: 0.001) and higher Child-Pugh scores (7.56 +/- 2.32 vs. 9.02 +/- 2.55, respectively; p: 0.004) when compared with cramp (-) patients. None of the serum related factors such as creatinine, calcium, magnesium, sodium, potassium, zinc, glucose, alanine aminotransferase, total bilirubin, and albumin levels had any statistically significant contribution to the etiology.

CONCLUSION: Muscle cramps are frequent complication of cirrhosis. Neither biochemical characteristics including decreased serum zinc levels nor the use of diuretics explained the greater prevalence of cramps in patients with cirrhosis. We conclude that the detrimental effect of cirrhosis on muscle fibers may be the major factor.

PURPOSE: The efficacy, safety, and cost of teriparatide in the treatment of osteoporosis are reviewed.

SUMMARY: Osteoporosis is a leading cause of fractures in women and men but is underdiagnosed and undertreated. Antiresorptive therapies (calcitonin, estrogen, bisphosphonates, and selective estrogen-receptor modulators) have historically been used to treat this condition. Teriparatide (recombinant human parathyroid hormone) is an anabolic agent labeled for use in postmenopausal women and men with osteoporosis who are at high risk for fractures. Clinical trials indicate that teriparatide increases predominantly trabecular bone in the lumbar spine and femoral neck; it has less significant effects at cortical sites. The combination of teriparatide with antiresorptive agents is not more effective than teriparatide monotherapy. The most common adverse effects associated with teriparatide include injection-site pain, nausea, headaches, leg cramps, and dizziness. After a maximum of two years of teriparatide therapy, the drug should be discontinued and antiresorptive therapy begun to maintain bone mineral density. Teriparatide is expensive but may be cost-effective in selected patients.

CONCLUSION: Teriparatideoffers a therapeutic option for patients at high risk of an osteoporotic fracture and for patients who are intolerant of or unresponsive to antiresorptive therapy.

Pyrazinamide is one of the first line drugs used for the treatment of tuberculosis. Hepatotoxicity and hyperuricaemia are important and common untoward effects seen after administration of pyrazinamide. The drug inhibits elimination of urates resulting in hyperuricaemia, the presenting features of which are arthralgia, arthritis or even gout. A-case of bilateral leg cramps due to hyperuricaemia following pyrazinamide therapy is reported here.

BACKGROUND: The use of diuretics, statins, and inhaled long-actingβ2-agonists (LABAs) is linked to muscle cramps but largely by anecdotal evidence. This study sought population-level data to better evaluate these associations.

METHODS: Linked health care databases containing prescribing information (December 1, 2000, to November 30, 2008) about 4.2 million residents of British Columbia, Canada, were evaluated using sequence symmetry analysis to determine in adults 50 years or older whether new quinine prescriptions (initiations of cramp treatment) increase in the year following diuretic, statin, or LABA starts. The statistic of interest was the sequence ratio: the number of quinine starts in the year following index drug introduction compared with the number of quinine starts in the preceding year (adjusted for age and time trends in population prescribing).

RESULTS: Adjusted sequence ratios (95% CIs) for the 3 drug classes were 1.47 (1.33-1.63 [P<.001]) for diuretics, 1.16 (1.04-1.29 [P = .004]) for statins, and 2.42 (2.02-2.89 [P<.001]) for LABAs. For diuretic subclasses,adjusted sequence ratios (95% CIs) were 2.12 (1.61-2.78 [P<.001]) for potassium sparing, 1.48 (1.29-1.68 [P<.001]) for thiazidelike, and 1.20 (1.00-1.44 [P = .07]) for loop. For LABA subclasses, adjusted sequence ratios (95% CIs) were 2.17 (1.56-3.02) for LABAs alone and 2.55 (2.06-3.12) for LABAs-corticosteroids (P<.001 for both).

CONCLUSIONS: Cramp treatment was substantially more likely in the year following introduction of LABAs, potassium-sparing diuretics, or thiazidelike diuretics, and 60.3% of quinine users (individuals experiencing cramp) received at least 1 of these medications during a 13-year period. In contrast, statin and loop diuretic associations were small. Physicians should be mindful that the use of these medications may worsen symptoms in patients experiencing nocturnal leg cramps.

Up to 60 percent of adults report that they have had nocturnal leg cramps. The recurrent, painful tightening usually occurs in the calf muscles and can cause severe insomnia. The exact mechanism is unknown, but the cramps are probably caused by muscle fatigue and nerve dysfunction rather than electrolyte or other abnormalities. Nocturnal leg cramps are associated with vascular disease, lumbar canal stenosis, cirrhosis, hemodialysis, pregnancy, and other medical conditions. Medications that are strongly associated with leg cramps include intravenous iron sucrose, conjugated estrogens, raloxifene, naproxen, and teriparatide. A history and physical examination are usually sufficient to differentiate nocturnal leg cramps from other conditions, such as restless legs syndrome, claudication, myositis, and peripheral neuropathy. Laboratory evaluation and specialized testing usually are unnecessary to confirm the diagnosis. Limited evidence supports treating nocturnal leg cramps with exercise and stretching, or with medications such as magnesium, calcium channel blockers, carisoprodol, or vitamin B(12). Quinine is no longer recommended to treat leg cramps.

Muscle cramps are a common problem characterized by a sudden, painful, involuntary contraction of muscle. These true cramps, which originate from peripheral nerves, may be distinguished from other muscle pain or spasm. Medical history, physical examination, and a limited laboratory screen help to determine the various causes of muscle cramps. Despite the "benign" nature of cramps, many patients find the symptom very uncomfortable. Treatment options are guided both by experience and by a limited number of therapeutic trials. Quinine sulfate is an effective medication, but the side-effect profile is worrisome, and other membrane-stabilizing drugs are probably just as effective. Patients will benefit from further studies to better define the pathophysiology of muscle cramps and to find more effective medications with fewer side-effects.