Medication Summary
Thiazides are specifically indicated for patients with renal leak hypercalciuria, in whom they not only reduce the inappropriate renal calcium loss but also lower parathyroid hormone (PTH) levels and normalize other metabolic processes. [62, 63]
These agents can also be used to treat absorptive hypercalciuria, but their long-term usefulness may diminish over time, requiring approximately 6 months of an alternative regimen before they are effective again.
Thiazides also increase serum calcium and uric acid levels while decreasing urinary citrate levels. Hyperuricemia and acute gout rarely develop in individuals receiving thiazides.
Because thiazide therapy carries the risk of inducing hypokalemia and hypocitraturia, potassium citrate supplements are often prescribed with thiazides in calcium-stone formers.
Diuretics, Thiazide
Class Summary
Thiazide diuretics are used in patients with hypercalciuria that is not adequately controlled with dietary modifications alone. Thiazide diuretics are also used upon evidence of bone demineralization if a patient’s diet includes less than the DRI of calcium.
Thiazides work by increasing calcium reabsorption at the level of the distal renal tubule and, thus, lowering urinary calcium. Hydrochlorothiazide (HCTZ) is the agent most commonly used, but other thiazide or thiazide-type diuretics can be administered, including trichlormethiazide and chlorthalidone.
Despite the common use of thiazides, no long-term clinical trials have been performed documenting their efficacy and safety in children. Parents should be notified of this and understand the risks and benefits before initiating therapy.
Hydrochlorothiazide (Microzide)
HCTZ is the most frequently used thiazide in the reduction of urinary calcium levels.
Chlorthalidone
This agent reduces calcium excretion through direct tubular effects.
Urinary Alkalinizing Agents
Class Summary
Potassium citrate is metabolized to bicarbonates, which increase urinary pH levels by increasing the excretion of free bicarbonate ions without producing systemic alkalosis when administered in recommended doses.
Potassium citrate (Urocit K)
This is an alkalinizing agent indicated for the treatment of systemic metabolic acidosis, urinary alkalinization, and hypocitraturia. Potassium citrate is administered orally and metabolized to bicarbonate in the liver.
Bisphosphonates
Class Summary
Drugs in this class increase bone deposition of calcium, thus removing it from the circulation before it can be excreted. This improves bone calcium density and helps to reduce urinary calcium levels. Bisphosphonates, such as alendronate (Fosamax), risedronate (Actonel), or ibandronate (Boniva), should be used in men and in women when estrogen cannot be used.
Pamidronate (Aredia)
The main action of pamidronate is to inhibit the resorption of bone. The mechanism by which this inhibition occurs is not fully known. The drug is adsorbed onto calcium pyrophosphate crystals and may block the dissolution of these crystals, also known as hydroxyapatite, which are an important mineral component of bone. Evidence also suggests that pamidronate directly inhibits osteoclasts.
Alendronate (Fosamax)
Alendronate is a potent third-generation bisphosphonate that principally acts by inhibiting osteoclastic bone resorption.
Ibandronate (Boniva)
Ibandronate inhibits the resorption of bone, increases bone mineral density, and reduces the incidence of vertebral fractures.
Risedronate (Actonel, Atelvia)
Risedronate is a potent aminobisphosphonate that principally acts by inhibiting osteoclastic bone resorption. It is recommended for the treatment of Paget disease.
Etidronate (Didronel)
Etidronate was the first bisphosphonate studied in humans and approved in the United States (1978) for the treatment of Paget disease. It is the least potent of currently available bisphosphonate drugs.
Tiludronate (Skelid)
Tiludronate is a sulfur-containing bisphosphonate of intermediate potency between etidronate and newer nitrogen-containing bisphosphonates. No food, indomethacin, or calcium should be ingested within 2 hours before and 2 hours after. A 3-month posttreatment evaluation follows.
Estrogen Derivatives
Class Summary
Estrogens should be used in postmenopausal women with hypercalciuria whenever possible. Their action is similar to that of the bisphosphonates.
Estrogens are used to increase the serum estrogen level, which, in turn, decreases the rate of bone resorption. The lowest effective dose at the shortest duration necessary should be used. Estrogen therapy reduces bone resorption and retards or halts postmenopausal bone loss. Estrogen therapy is no longer a first-line approach for the treatment of osteoporosis in postmenopausal women because of increased risk of breast cancer, stroke, venous thromboembolism, and coronary disease. The FDA recommends that other approved nonestrogen treatments be considered first for osteoporosis prevention.
Conjugated estrogens (Premarin)
Estrogens can directly affect bone mass through estrogen receptors in bone, reducing bone turnover and bone loss. Estrogens can also indirectly increase intestinal calcium absorption and renal calcium conservation and, therefore, improve calcium balance. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should be considered only for women at significant risk of osteoporosis and for whom nonestrogen medications need to be carefully considered.
Estradiol (Estrace, Estraderm, Menostar, Vivelle-Dot, Climara, Estraderm, Alora)
Estradiol restores estrogen levels to concentrations that induce negative feedback at gonadotropic regulatory centers; this, in turn, reduces the release of gonadotropins from the pituitary. Estradiol increases the synthesis of DNA, RNA, and many proteins in target tissues; it also inhibits osteoclastic activity and delays bone loss. In addition, evidence suggests a reduced incidence of fractures.
Estropipate (Ortho-Ext 0.625, Ortho-Est 1.25)
Estropipate is indicated for the prevention of osteoporosis. When estrogen therapy is discontinued, bone mass declines at a rate comparable to that of the immediate postmenopausal period. No evidence suggests that estrogen replacement therapy restores bone mass to premenopausal levels.
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Calcium-rich foods.
Tables
Diet |
Definition |
Regular diet (unrestricted) |
Women: Urinary excretion >250 mg calcium (6.2 mmol/24 h) Men: Urinary excretion >275-300 mg calcium (7.5 mmol/24 h) |
Urinary excretion >4 mg calcium (0.1 mmol) per kilogram of body weight per day Urinary concentration >200 mg calcium per liter |
|
Restricted diet (400 mg calcium, 100 mEq sodium) |
Urinary excretion >200 mg calcium per day |
Urinary excretion >3 mg calcium per kilogram of body weight per day |
Hypercalciuria Diagnosis |
Urinary Calcium on 400-mg Calcium Diet (Normal = < 200 mg/24 h) |
Fasting Calcium/Creatinine (mg/dL) Ratio (Normal = < 0.11) |
Post–Calcium Load Calcium/Creatinine Ratio (Normal = < 0.20) |
Normal |
Normal |
Normal |
Normal |
Absorptive type I |
High |
Normal |
High |
Absorptive type II |
Normal |
Normal |
High |
Absorptive type III (renal phosphate leak) |
High |
High |
High |
Renal leak |
High |
High |
High |
Resorptive (hyperparathyroidism) |
High |
High |
High |
Criteria |
Absorptive Type I Vitamin D–Dependent (Classic Form) |
Absorptive Type I Vitamin D–Dependent (Variant Form) |
Absorptive Type II Dietary Calcium Responsive |
Absorptive Type III (Renal Phosphate Leak) |
Renal Calcium Leak |
Resorptive |
Urinary calcium on regular diet* |
High |
High |
High |
High |
High |
High |
Urinary calcium on low-calcium diet† |
High |
High |
NL |
High |
High |
High |
Urinary calcium fasting‡ |
NL |
High |
NL |
High |
High |
High |
Urinary calcium after 1-g calcium load§ |
High |
High |
NL |
High |
High |
High |
Serum PO4 (fasting) |
NL |
NL |
NL |
Low |
NL or high |
Low |
Serum calcium (fasting) |
NL |
NL or high |
NL |
NL or high |
NL or low |
High |
Serum PTH |
NL or low |
NL or low |
NL |
Low |
High |
High |
Serum PTH after 1-g calcium load |
NL or low |
NL or low |
NL |
Low |
High |
High |
Serum vitamin D3 (calcitriol) |
NL |
High |
NL |
High |
High |
High |
Fasting normocalciuria while on ketoconazole |
No |
Yes |
No |
Yes |
No |
No |
Bone calcium density |
NL |
NL or low |
NL |
NL or low |
Low |
Low |
NL = normal; PO4 = phosphate; PTH = parathyroid hormone. * Regular diet is unrestricted calcium and sodium intake. Normal upper limit calciuria is < 4 mg/kg body weight per day. † Low-calcium diet is 400 mg calcium and 100 mEq of sodium per day. Normal upper limit calciuria is < 200 mg/day. ‡ Fasting is a 12-hour fast. Normal upper limit is < 0.11 mg calcium/mg creatinine. § After 1-g calcium load, normal upper limit is < 0.20 mg calcium/mg creatinine. |
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