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Corrected calcium  / MOA / List of agents

Corrected calcium= serum calcium + 0.8 (4 - serum albumin)

Bisphosphonates inhibit bone resorption via actions on osteoclasts or on osteoclast precursors which leads to decreases in the rate of bone resorption and an indirect increase in bone mineral density.

Bisphosphonates and other agents used for treatment of Osteoporosis
alendronate (Fosamax ®):
etidronate (Didronel ®)
ibandronate (Boniva ®)
pamidronate (Aredia ®)
risedronate (Actonel ®)
tiludronate (Skelid ®)
Zoledronic acid (Zometa®)

Osteoporosis - other:
Raloxifene (Evista®)
Teriparatide (Forteo®)


Alendronate (fosamax ®) 

Dosing (Adults): 
Osteoporosis in postmenopausal females: Oral: Prophylaxis: 5 mg once daily or 35 mg once weekly.  Treatment: 10 mg once daily or 70 mg once weekly.
Osteoporosis in males: Oral: 10 mg once daily or 70 mg once weekly.

Osteoporosis secondary to glucocorticoids in males and females: Oral: Treatment: 5 mg once daily; a dose of 10 mg once daily should be used in postmenopausal females who are not receiving estrogen.

Paget's disease of bone in males and females: Oral: 40 mg once daily for 6 months.
Retreatment: Relapses during the 12 months following therapy occurred in 9% of patients who responded to treatment. Specific retreatment data are not available. Following a 6-month post-treatment evaluation period, treatment with alendronate may be considered in patients who have relapsed based on increases in serum alkaline phosphatase, which should be measured periodically. Retreatment may also be considered in those who failed to normalize their serum alkaline phosphatase.

Renal Dosing:
CrCl <35 ml/minute: Alendronate is not recommended due to lack of experience.

May cause esophagitis. Alendronate should be taken in the morning with a full glass (eg, 6 to 8 ounces) of plain water at least one-half hour before food, beverages, or other medications.

Oral Solution:  70 mg/75 ml.  Tablet: 5 mg, 10 mg, 35 mg, 40 mg, 70 mg.

Etidronate (didronel ®)  

Dosing (Adults)
Oral formulation should be taken on an empty stomach 2 hours before any meal.
Paget's disease: Oral:   Initial: 5-10 mg/kg/day (not to exceed 6 months) or 11-20 mg/kg/day (not to exceed 3 months). Doses >10 mg/kg/day are not recommended.  Retreatment: Initiate only after etidronate-free period >/= 90 days. Monitor patients every 3-6 months. Retreatment regimens are the same as for initial treatment.

Heterotopic ossification: Oral:  Caused by spinal cord injury: 20 mg/kg/day for 2 weeks, then 10 mg/kg/day for 10 weeks; total treatment period: 12 weeks

Complicating total hip replacement: 20 mg/kg/day for 1 month preoperatively then 20 mg/kg/day for 3 months postoperatively; total treatment period is 4 months

Hypercalcemia associated with malignancyI.V. (dilute dose in at least 250 mL NS): 7.5 mg/kg/day for 3 days; there should be at least 7 days between courses of treatment.  Oral: Start 20 mg/kg/day on the last day of infusion and continue for 30-90 days

Dosing adjustment in renal impairment:
Scr 2.5-5 mg/dL: Use with caution
Scr >5 mg/dL: Not recommended

Injection, solution: 50 mg/mL (6 mL)
Tablet: 200 mg, 400 mg

Ibandronate(boniva ®) 


Dosing (Adults): (usual):
Treatment of postmenopausal osteoporosis
: 2.5 mg orally once day or 150 mg once a month.
Prevention of postmenopausal osteoporosis: 2.5 mg orally once daily. 150 mg once a month may be considered.

Supplied: 2.5 mg tablet (once-daily formulation), 150 mg tablet - (once-monthly formulation).

Pamidronate (aredia ®)  

Dosing (Adults)
Drug must be diluted properly before administration and infused intravenously slowly. Due to risk of nephrotoxicity, doses should not exceed 90 mg.

Hypercalcemia of malignancy
Moderate cancer-related hypercalcemia (corrected serum calcium: 12-13.5 mg/dL): 60-90 mg, as a single dose, given as a slow infusion over 2-24 hours; dose should be diluted in 1000 mL 0.45% NaCl, 0.9% NaCl, or D5W.    
Severe cancer-related hypercalcemia
(corrected serum calcium: >13.5 mg/dL): 90 mg, as a single dose, as a slow infusion over 2-24 hours; dose should be diluted in 1000 mL 0.45% NaCl, 0.9% NaCl, or D5W.

A period of 7 days should elapse before the use of second course; repeat infusions every 2-3 weeks have been suggested, however, could be administered every 2-3 months according to the degree and of severity of hypercalcemia and/or the type of malignancy.

Note: Some investigators have suggested a lack of a dose-response relationship. Courses of pamidronate for hypercalcemia may be repeated at varying intervals, depending on the duration of normocalcemia (median 2-3 weeks), but the manufacturer recommends a minimum interval between courses of 7 days. Oral etidronate at a dose of 20 mg/kg/day has been used to maintain the calcium lowering effect following I.V. bisphosphonates, although it is of limited effectiveness.

Osteolytic bone lesions with multiple myeloma: 90 mg in 500 mL D5W, 0.45% NaCl or 0.9% NaCl administered over 4 hours on a monthly basis.

Osteolytic bone lesions with metastatic breast cancer: 90 mg in 250 mL D5W, 0.45% NaCl or 0.9% NaCl administered over 2 hours, repeated every 3-4 weeks

Paget's disease: 30 mg in 500 mL 0.45% NaCl, 0.9% NaCl or D5W administered over 4 hours for 3 consecutive days

Dosing adjustment in renal impairment: Not recommended in severe renal impairment (patients with bone metastases).      Dosing adjustment in renal toxicity: In patients with bone metastases, treatment should be withheld in patients who experience deterioration in renal function (increase of serum creatinine >/= 0.5 mg/dL in patients with normal baseline or >/= 1.0 mg/dL in patients with abnormal baseline). Resumption of therapy may be considered when serum creatinine returns to within 10% of baseline.

Injection, powder for reconstitution, as disodium (Aredia®): 30 mg, 90 mg
Injection, solution: 3 mg/mL (10 mL); 6 mg/mL (10 mL); 9 mg/mL (10 mL)

Risedronate (actonel ®)  

Dosing (Adults)
Risedronate should be taken at least 30 minutes before the first food or drink of the day other than water. Oral:  Adults (patients should receive supplemental calcium and vitamin D if dietary intake is inadequate):
Paget's disease of bone: 30 mg once daily for 2 months.    Retreatment may be considered (following post-treatment observation of at least 2 months) if relapse occurs, or if treatment fails to normalize serum alkaline phosphatase. For retreatment, the dose and duration of therapy are the same as for initial treatment. No data are available on more than one course of retreatment.

Osteoporosis (postmenopausal) prevention and treatment: 5 mg once daily; efficacy for use longer than 1 year has not been established; alternatively, a dose of 35 mg once weekly has been demonstrated to be effective

Osteoporosis (glucocorticoid-induced) prevention and treatment: 5 mg once daily

Elderly: Dosage adjustment is not necessary in patients with Clcr >/= 30 mL/minute.

Renal dosing:
Dosage adjustment in renal impairment: Clcr<30 mL/minute: Not recommended for use

Should be taken on an empty stomach in an upright position with at least 6 ounces of plain water. The upright position and empty stomach should be maintained for at least 30 minutes to minimize gastrointestinal adverse events and increase absorption.

 [Supplied: 5 mg, 30 mg, 35 mg tablet]

Tiludronate (skelid ®)  

Dosing (Adults)
Tiludronate should be taken with 6-8 oz of plain water and not taken within 2 hours of food.

Treatment of Paget's disease of the bone in patients who have a level of serum alkaline phosphatase (SAP) at least twice the upper limit of normal, or who are symptomatic, or who are at risk for future complications of their disease:    Oral: 400 mg (2 tablets of tiludronic acid) daily for a period of 3 months; allow an interval of 3 months to assess response

Dosing adjustment in renal impairment: Clcr<30 mL/minute: Not recommended

200 mg tablet[equivalent to 240 mg tiludronate disodium]

Zoledronic acid (zometa®)  

Dosing (Adults)
(usual): Hypercalcemia of malignancy: 4 mg IV given as a single dose infusion over no less than 15 min; may repeat after a minimum of 7 days if serum calcium does not return to normal or remain normal after initial treatment.
Multiple myeloma/metastatic bone lesions from solid tumors: 4 mg IV infused over 15 min every 3-4 weeks; administer with an oral calcium supplement of 500 mg and a multiple vitamin containing 400 International Units of vitamin D.
Paget's disease: 100-400 mcg as a single infusion infused over 1 hr.

Vigorous saline hydration alone may be sufficient to treat mild, asymptomatic hypercalcemia. The maximum recommended dose of Zometa in hypercalcemia of malignancy (albumin-corrected serum calcium * >/=12 mg/dL [3.0 mmol/L]) is 4 mg. The 4-mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes. Patients should be adequately rehydrated prior to administration of Zometa. Renal function must be carefully monitored in all patients receiving Zometa and possible deterioration in renal function must be assessed prior to retreatment with Zometa.

Raloxifene (evista®)  

Dosing (Adults): (usual):
Osteoporosis prevention: 60 mg orally qd.
Osteoporosis treatment: 60 mg orally qd.

Treatment and Prevention of Osteoporosis in Postmenopausal Women: EVISTA is indicated for the treatment and prevention of osteoporosis in postmenopausal women.

Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women with Osteoporosis: EVISTA is indicated for the reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis.

Reduction in the Risk of Invasive Breast Cancer in Postmenopausal Women at High Risk of Invasive Breast Cancer: EVISTA is indicated for the reduction in risk of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer. The effect in the reduction in the incidence of breast cancer was shown in a study of postmenopausal women at high risk for breast cancer with a 5-year planned duration with a median follow-up of 4.3 years [see Clinical Studies]. Twenty-seven percent of the participants received drug for 5 years. The long-term effects and the recommended length of treatment are not known.

High risk of breast cancer is defined as at least one breast biopsy showing lobular carcinoma in situ (LCIS) or atypical hyperplasia, one or more first-degree relatives with breast cancer, or a 5-year predicted risk of breast cancer ≥ 1.66% (based on the modified Gail model). Among the factors included in the modified Gail model are the following: current age, number of first-degree relatives with breast cancer, number of breast biopsies, age at menarche, nulliparity or age of first live birth. Healthcare professionals can obtain a Gail Model Risk Assessment Tool by dialing 1-800-545-5979. Currently, no single clinical finding or test result can quantify risk of breast cancer with certainty.

After an assessment of the risk of developing breast cancer, the decision regarding therapy with EVISTA should be based upon an individual assessment of the benefits and risks.

EVISTA does not eliminate the risk of breast cancer. Patients should have breast exams and mammograms before starting EVISTA and should continue regular breast exams and mammograms in keeping with good medical practice after beginning treatment with EVISTA.

Important Limitations of Use for Breast Cancer Risk Reduction

* There are no data available regarding the effect of EVISTA on invasive breast cancer incidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of EVISTA.
* EVISTA is not indicated for the treatment of invasive breast cancer or reduction of the risk of recurrence.
* EVISTA is not indicated for the reduction in the risk of noninvasive breast cancer.

Dosing (Adults): (usual):
The recommended dosage is one 60 mg EVISTA tablet daily, which may be administered any time of day without regard to meals.

Supplied: 60 mg tablet

Teriparatide (forteo®) 

Mechanism of Action
Endogenous 84-amino acid parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidney. Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. The biological actions of PTH and teriparatide are mediated through binding to specific high-affinity cell-surface receptors. Teriparatide and the 34 N-terminal amino acids of PTH bind to these receptors with the same affinity and have the same physiological actions on bone and kidney. Teriparatide is not expected to accumulate in bone or other tissues.

The skeletal effects of teriparatide depend upon the pattern of systemic exposure. Once-daily administration of teriparatide stimulates new bone formation on trabecular and cortical (periosteal and/or endosteal) bone surfaces by preferential stimulation of osteoblastic activity over osteoclastic activity. In monkey studies, teriparatide improved trabecular microarchitecture and increased bone mass and strength by stimulating new bone formation in both cancellous and cortical bone. In humans, the anabolic effects of teriparatide manifest as an increase in skeletal mass, an increase in markers of bone formation and resorption, and an increase in bone strength. By contrast, continuous excess of endogenous PTH, as occurs in hyperparathyroidism, may be detrimental to the skeleton because bone resorption may be stimulated more than bone formation.

Dosing (Adults)
Treatment of osteoporosis in postmenopausal women at high risk of fracture; treatment of primary or hypogonadal osteoporosis in men at high risk of fracture:  20 mcg  SubQ once daily; Note: Initial administration should occur under circumstances in which the patient may sit or lie down, in the event of orthostasis.

Dosage adjustment in renal impairment: No dosage adjustment required. Bioavailability and half-life increase with Clcr<30 mL/minute.

Injection, solution: 250 mcg/mL (3 mL) [prefilled syringe, delivers teriparatide 20 mcg/dose]



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