MEDICAL POLICY
POLICY TITLE
INJECTABLE BISPHOSPHONATES FOR THE TREATMENT OF
PAGET’S DISEASE AND CANCER RELATED INDICATIONS
POLICY NUMBER
MP- 2.132
Original Issue Date (Created):
November 1, 2008
Most Recent Review Date
(Revised):
December 16, 2008
Effective Date:
January 31, 2010- RETIRED
I.
DESCRIPTION/BACKGROUND
Zoledronic acid (Zometa®, Reclast®) and pamidronate disodium (Aredia®) are
injectable bisphosphonates that inhibit the resorption and reformation of bone.
Bisphosphonates help prevent damaging changes to the bone caused by Paget’s disease of
bone, bone metastases and medications that decrease bone mineral density (BMD).
Bone metastasis is the spread of cancer from a primary site to the bone. Common areas
of metastasis include the spine, pelvis, hip, femur, and skull. Portions of bone wear away,
leaving small holes called osteolytic bone lesions. Bone metastasis can also cause
abnormal weak and unstable bone formation called osteoblastic bone lesions. Affected
bones are prone to fracture resulting in pain and decreased mobility. Vertebral fractures
can cause spinal cord compression and subsequent paralysis. Hypercalcemia, a late
complication of cancer, can cause nausea and vomiting, dehydration, coma, and death.
Bisphosphonates can also reduce blood calcium levels by preventing release of calcium
from the bones.
Paget’s disease of bone (osteitis deformans) is a chronic disease of the bone characterized
by excessive osteoclastic bone resorption followed by excessive bone formation.
Affected bones are thick but structurally weak and prone to fractures or deformity.
Paget's disease occurs most frequently in the spine, skull, pelvis and bones of the lower
extremities. One or more bones may be affected. Paget's disease is rarely diagnosed in
people less than 40 years of age.
There are medications used to treat specific cancers, which will decrease BMD. These
include aromatase inhibitors (exemestane, anastrozole, letrozole, etc) used to treat
hormone-dependent breast cancer and androgen deprivation therapy used to treat prostate
cancer. Zoledronic acid has been shown to increase BMD in those with clinically
significant bone loss due to these medications.
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MEDICAL POLICY
POLICY TITLE
INJECTABLE BISPHOSPHONATES FOR THE TREATMENT OF
PAGET’S DISEASE AND CANCER RELATED INDICATIONS
POLICY NUMBER
MP- 2.132
Baseline bone mineral density and follow up monitoring are warranted when injectable
bisphosphonates are being considered or used to prevent loss of BMD due to cancer
treatment drugs.
Zometa® (zoledronic acid) has been approved by the Federal Drug Administration
(FDA) for the treatment of hypercalcemia of malignancy (HCM). It is also FDA
approved for the treatment of patients with multiple myeloma and patients with
documented bone metastases from solid tumors, in conjunction with standard
antineoplastic therapy. Reclast® (zoledronic acid) has been FDA approved for the
treatment of Paget’s disease of the bone and postmenopausal osteoporosis.
Aredia® (pamidronate disodium) has been FDA approved for the treatment of moderate
or severe hypercalcemia associated with malignancy, with or without bone metastases,
Paget’s disease, osteolytic bone metastases of breast cancer and osteolytic lesions of
multiple myeloma.
II.
DEFINITIONS
ANTINEOPLASTIC AGENTS are substances that inhibit or prevent the growth of neoplasms.
MYELOMA is a malignant tumor composed of plasma cells of the type normally found in the
bone marrow.
OSTEOCLASTIC refers to osteoclasts, especially with reference to their activity in the
absorption and removal of osseous (bone) tissue.
OSTEOPENIA is a condition of subnormally mineralized bone, usually the result of a rate of
bone lysis that exceeds the rate of bone matrix synthesis. It is defined as a BMD between –
1.0 and –2.5.
III.
POLICY
Note: This policy pertains to coverage of injectable bisphosphonates for the treatment of
Paget’s disease and cancer related indications only.*
Pamidronate (Aredia®) may be considered medically necessary for any of the following
indications:
 Hypercalcemia associated with malignancy.
 Paget's disease of bone characterized by abnormal and accelerated bone metabolism.
 Osteolytic bone metastases of breast cancer.
 Osteolytic lesions of multiple myeloma in conjunction with standard antineoplastic
therapy.
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MEDICAL POLICY
POLICY TITLE
INJECTABLE BISPHOSPHONATES FOR THE TREATMENT OF
PAGET’S DISEASE AND CANCER RELATED INDICATIONS
POLICY NUMBER
MP- 2.132
Zoledronic acid (Zometa®) may be considered medically necessary for any of the
following indications:
 Hypercalcemia of malignancy
 Multiple Myeloma
 Bone Metastases from solid tumors:
o Breast cancer
o Lung cancer
o Prostate cancer (if cancer has progressed after treatment with at least one hormonal
therapy)
o Other solid tumor types
Zoledronic acid (Reclast®) may be considered medically necessary for the following
indication:
 Paget’s disease of bone
* Note: See MP-2.131 for additional indications for Aredia®, Zometa® and Reclast®
including osteopenia or osteoporosis caused by cancer therapy.
Cross Reference: MP-2.131 Injectable Bishosphonates for the Treatment of Osteoporosis
IV.
EXCLUSIONS
The use of injectable bisphosphonates for non-FDA approved indications is considered
investigational, as there is insufficient evidence to support a conclusion concerning the
health outcomes or benefits associated with this procedure.
V.
BENEFIT VARIATIONS
The existence of this medical policy does not mean that this service is a covered benefit
under the member's contract. Benefit determinations should be based in all cases on the
applicable contract language. Medical policies do not constitute a description of benefits.
A member’s individual or group customer benefits govern which services are covered,
which are excluded, and which are subject to benefit limits and which require
preauthorization. Members and providers should consult the member’s benefit information
or contact Capital for benefit information.
VI.
DISCLAIMER
Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute
medical advice and are subject to change. Treating providers are solely responsible for medical advice and
treatment of members. Members should discuss any medical policy related to their coverage or condition
with their provider and consult their benefit information to determine if the service is covered. If there is a
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[Note: Final page is signature page and is kept on file, but not issued with Policy.]
MEDICAL POLICY
POLICY TITLE
INJECTABLE BISPHOSPHONATES FOR THE TREATMENT OF
PAGET’S DISEASE AND CANCER RELATED INDICATIONS
POLICY NUMBER
MP- 2.132
discrepancy between this medical policy and a member’s benefit information, the benefit information will
govern. Capital considers the information contained in this medical policy to be proprietary and it may only
be disseminated as permitted by law.
VII. REFERENCES
Aredia prescribing information. [Website]: http://www.drugs.com/pro/aredia.html .
Accessed October 6, 2008.
Berenson J, Kyle R. Risks of bisphosphonate therapy in patients with malignancy.
UpToDate. Version 15.3. Updated June14, 2007. [Website]:
http://www.utdol.com/utd/content/topic.do?topicKey=genl_onc/17310&selectedTitle=4
~150&source=search_result . Accessed October 6, 2008.
Bilezikian JP. Osteonecrosis of the Jaw — Do Bisphosphonates Pose a Risk? N Engl J Med
355:2278, November 30, 2006.
Centers for Medicare and Medicaid Services (CMS). CMS On-Line Manual Pub. 100-2,
Chapter 15, Section 50. Drugs and Biologicals. [Website]:
http://www.cms.hhs.gov/manuals/Downloads/bp102c15.pdf . Accessed October 6,
2008.
Chow D, Slipman C, Braverman D. Paget Disease. EMedicine. Updated August 3, 2007.
[Website]: http://www.emedicine.com/pmr/topic98.htm . Accessed October 6, 2008.
Clemons M, Dranitsaris G, Cole D, Gainford M. Too Much, Too Little, Too Late to Start
Again? Assessing the Efficacy of Bisphosphonates in Patients with Bone Metastases
from Breast Cancer. Oncologist, Mar 2006; 11: 227 – 233.
Coleman R. Bisphosphonates: Clinical Experience Oncologist, Sep 2004; 9: 14 - 2.
Costa L. Bisphosphonates: Reducing the risk of skeletal complications from bone
metastasis. Breast. 2007 Nov 19.
Devogelaer JP, Manicourt DH.Zoledronic acid for treatment of Paget's disease of bone.
Expert Opin Pharmacother. 2007 Nov;8(16):2863-9.
ECRI. Custom Hotline Report. Zoledronic Acid (Zometa) use in cancer treatment. Updated
December 2007.
Gridelli C. The Use of Bisphosphonates in Elderly Cancer Patients. Oncologist, Jan 2007;
12: 62 – 71.
Highmark Medicare Services Local Coverage Determination (LCD)L27473: Approved
Drugs and Biologicals. Effective 12/12/08. [Website]:
http://www.highmarkmedicareservices.com/policy/mac-ab/l27473-r4.html. Accessed
January 22, 2009.
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MEDICAL POLICY
POLICY TITLE
INJECTABLE BISPHOSPHONATES FOR THE TREATMENT OF
PAGET’S DISEASE AND CANCER RELATED INDICATIONS
POLICY NUMBER
MP- 2.132
Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003
update on the role of bisphosphonates and bone health issues in women with breast
cancer. J Clin Oncol 2003 Nov 1;21(21):4042-57. [Website]:
http://www.guideline.gov/summary/summary.aspx?doc_id=4541&nbr=003355&string
=breast+AND+bisphosphonate . Accessed October 6, 2008.
Keating GM, Scott LJ. Zoledronic acid: A review of its use in the treatment of Paget's
disease of bone. Drugs. 2007;67(5):793-804.
Kelepouris N. Treatment of Paget’s disease of bone. UpToDate. Version 15.3. Updated
April 30, 2007. [Website]
http://www.utdol.com/utd/content/topic.do?topicKey=othrheum/12209&selectedTitle=
6~150&source=search_result . Accessed October 6, 2008.
Kyle R, Berenson J. The use of bisphosphonates in patients with multiple myeloma.
UpToDate. Version 15.3. Updated June14, 2007. [Website]:
http://www.utdol.com/utd/content/topic.do?topicKey=plasma/8070&selectedTitle=3~1
50&source=search_result. Accessed October 6, 2008.
Kyle RA, Yee GC, Somerfield MR. American Society of Clinical Oncology 2007 clinical
practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin
Oncol. 2007 Jun 10;25(17):2464-72. [Website]:
http://www.guideline.gov/summary/summary.aspx?doc_id=10857&nbr=005670&strin
g=myeloma . Accessed October 6, 2008.
Lacy MQ, Dispenzieri A, Gertz MA, et al. Mayo clinic consensus statement for the use of
bisphosphonates in multiple myeloma. Mayo Clin Proc. 2006;81(8):1047-1053.
Novartis Pharmaceuticals Corporation. Zometa (zoledronic acid for injection) product
labeling. Novartis; 2002. [Website]:
http://www.fda.gov/cder/foi/label/2002/21386lbl.pdf. Accessed October 6, 2008.
Novartis Pharmaceuticals Corporation. Reclast (zoledronic acid for injection) product
labeling. Novartis; 2007. [Website]:
http://www.fda.gov/cder/foi/label/2007/021817lbl.pdf. Accessed October 6, 2008.
On-line Medical Dictionary, CancerWeb [Website]: http://cancerweb.ncl.ac.uk/omd/ .
Accessed October 6, 2008.
Pavlakis N, Schmidt R, Stockler M. Bisphosphonates for breast cancer. Cochrane
Database Syst Rev. 2005;(3):CD003474.
Riccio A, Wodajo F, Malawer M. Metastatic Carcinoma of the Long Bones. Am Fam
Physician 2007; 76:1489-94.
Savarese D, Berenson J. Bisphosphonates in breast, prostate and other cancers.
UpToDate. Version 15.3. Updated July 31, 2007. [Website]:
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[Note: Final page is signature page and is kept on file, but not issued with Policy.]
MEDICAL POLICY
POLICY TITLE
INJECTABLE BISPHOSPHONATES FOR THE TREATMENT OF
PAGET’S DISEASE AND CANCER RELATED INDICATIONS
POLICY NUMBER
MP- 2.132
http://www.utdol.com/utd/content/topic.do?topicKey=breastcn/2270&selectedTitle=2~
150&source=search_result . Accessed October 6, 2008.
Siris ES, Lyles KW, Singer FR, Meunier PJ. Medical management of Paget's disease of
bone: Indications for treatment and review of current therapies. J Bone Miner Res.
2006;21 Suppl 2:P94-P98.
The Paget Foundation. A Physician’s Guide to The Mangement of Paget’s Disease of
Bone. 2007. [Website]: http://www.paget.org/pdf/paget-mgt2007.pdf . Accessed
October 6, 2008.
The Paget Foundation. Bisphosphonates Fact Sheet. [Website]:
http://www.paget.org/Information/FactSheet/bisfact.html . Accessed October 6, 2008.
Theriault RL, Biermann JS, Brown E, et al. NCCN Task Force Report: Bone Health and
Cancer Care. J Natl Compr Canc Netw. 2006 May;4 Suppl 2:S1-20.
Wong R, Shukla VK, Mensinkai S, Wiffen P. Bisphosphonate agents for the managementof
pain secondary to bone metastases: a systematic review of effectiveness and safety.
Ottawa: Canadian Coordinating Office for Health Technology Assessment; 2004.
Technology report no 45. [Website]:
http://www.cadth.ca/media/pdf/170_bisphosphonate_tr_e.pdf. Accessed October 6,
2008.
Yuen KK, Shelley M, Sze WM, Wilt T, Mason MD. Bisphosphonates for advanced prostate
cancer. Cochrane Database Syst Rev 2006;(4):CD006250.
VIII. PRODUCT VARIATIONS
[N] = No product variation, policy applies as stated
[Y] = Standard product coverage varies from application of this policy, see below
[N] CHIP POS
[N] Indemnity
[N] PPO
[N] SpecialCare
[N] HMO
[N] POS
[N] CHIP HMO
[N] FEP HMO
[Y] SeniorBlue*
[N] FEP PPO
[Y] SeniorBlue PPO*
* Refer to Highmark Medicare Services LCD L27473 Approved Drugs and Biologicals.
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[Note: Final page is signature page and is kept on file, but not issued with Policy.]
MEDICAL POLICY
POLICY TITLE
INJECTABLE BISPHOSPHONATES FOR THE TREATMENT OF
PAGET’S DISEASE AND CANCER RELATED INDICATIONS
POLICY NUMBER
MP- 2.132
IX.
CODING INFORMATION
Note: This list of codes may not be all-inclusive, and codes are subject to change at any
time. The identification of a code in this section does not denote coverage as
coverage is determined by the terms of member benefit information. In addition, not
all covered services are eligible for separate reimbursement.
J2430
J3487
J3488
Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance
Company® and Keystone Health Plan® Central. Independent licensees of the Blue Cross and Blue Shield Association.
Communications issued by Capital BlueCross in its capacity as administrator of programs and provider relations for all companies.
IX.
POLICY HISTORY
MP-2.132
CAC 1/29/08 New Policy
CAC 11/25/08
Policy approved for retirement 1/31/10. This was last version of MP 2.132 that
was used. Information separated into separate medical policies- 2.131 & 2.143.
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