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Thursday, July 20, 2006
Bone metastases
Breast cancer. For the majority of patients with stage I or II breast cancer, bone scans are considered
optional at diagnosis, and routine bone scans in asymptomatic patients provide no advantage in survival or
ability to palliate recurrent disease.[65]=National Comprehensive Cancer Network. Clinical practice
guidelines in oncology, breast cancer, v.2.2006. National Comprehensive Cancer Network; 2004.
Prostate cancer
Cancer Network guidelines recommend a bone scan at diagnosis for T1 to T2 disease in the presence of a PSA
level >20 ng/mL, a Gleason score of >/=8, T3 to T4, or symptomatic disease.
ASCO Screening Recommendations for Cancer Treatment-Related Bone Loss in Women With Localized Breast
Cancer
Initial screening
* All women aged 65 years or older
* All women aged 60 to 64 years with
– Family history of fragility fracture
– Body weight <70 kg
– Prior nontraumatic fracture
– Other risk factors
* Postmenopausal women of any age receiving aromatase inhibitors
* Premenopausal women with therapy-associated premature menopause
Repeat BMD annually after initial examination.
Bisphosphonates are divided into 2 classes based on their chemical structure and mechanism of action—
nitrogen-containing bisphosphonates (ie, alendronate, ibandronate, pamidronate, risedronate, zoledronic
acid) and non–nitrogen-containing bisphosphonates (ie, clodronate, etidronate).[92] Nitrogen-containing
bisphosphonates are more potent than non–nitrogen-containing bisphosphonates because they inhibit the
enzyme farnesyl diphosphate synthase, an enzyme in the cholesterol biosynthesis pathway.
During bone formation, the biochemical markers released into the circulation include bone-specific ALP,
the procollagen extension peptides (PICP, PINP), and OC.[7,68] ALP and OC are measured in serum. Bone
resorption leads to collagen breakdown and results in the release of bone resorption markers into the
circulation, including NTx, CTx, Pyr, and DPD.
Commonly used radiopharmaceuticals include strontium chloride-89, sodium phosphate-32, and samarium-153
lexidronam. In patients with bone metastases, radiopharmaceuticals may be used as an alternative or
adjunct to external beam radiation therapy.[84,85] These agents are not useful in spinal cord or
peripheral nerve invasion by adjacent metastases, for acute pathologic fractures, or for pure osteolytic
lesions.
Table 4. Proposed Scoring System for Predicting Risk of Pathologic Fracture Through a Metastatic Lesion in
a Long Bone. Reprinted with permission from Mirels H et al. Clin Orthop Relat Res. 1989;249:256-265.
Points
1 2 3
Image Blastic Mixed Lytic
Size <1/3 1/3 to 2/3 >2/3
Site Upper extremity Lower extremity Peritrochanteric
Pain Mild Moderate Mechanical
This system grades each of 4 radiographic and clinical risk factors on a scale of 1 to 3. The authors
suggest that lesions with a cumulative score of 7 or less can be safely irradiated without risk of
fracture, while a score of 8 or higher (higher risk of fracture) should prompt prophylactic internal
fixation prior to irradiation.
Disease-free and overall survival were significantly better with clodronate. With longer follow-up (103 ±
12 months), the incidence of osseous and visceral metastases was similar in both groups.[103] A difference
in disease-free survival could no longer be demonstrated; however, overall survival was still
significantly better with clodronate (P < .01). The authors concluded that adjuvant clodronate therapy
prolongs survival in patients with breast cancer.[103]=# Jaschke A, Bastert G, Solomayer EF, et al.
Adjuvant clodronate treatment improves the overall survival of primary breast cancer patients with
micrometastases to bone marrow—a longtime follow-up. Proc Am Soc Clin Oncol. 2004;23:9. Abstract 529.
Osteonecrosis of the jaw (ONJ) is a serious dental condition that has been reported inpatients receiving
IV and, to a lesser extent, oral bisphosphonates.114,115 Incidence has been reported in a recent large,
retrospective review series at 0.6%.[116]=Van Poznak CH, Estilo CL, Sauter NP, et al. Osteonecrosis of the
jaw in patients with metastic breast cancer. Presented at 27th Annual Breast Cancer Symposium; December 9,
2004; San Antonio, Tex. Abstract 3057.
Medscape
optional at diagnosis, and routine bone scans in asymptomatic patients provide no advantage in survival or
ability to palliate recurrent disease.[65]=National Comprehensive Cancer Network. Clinical practice
guidelines in oncology, breast cancer, v.2.2006. National Comprehensive Cancer Network; 2004.
Prostate cancer
Cancer Network guidelines recommend a bone scan at diagnosis for T1 to T2 disease in the presence of a PSA
level >20 ng/mL, a Gleason score of >/=8, T3 to T4, or symptomatic disease.
ASCO Screening Recommendations for Cancer Treatment-Related Bone Loss in Women With Localized Breast
Cancer
Initial screening
* All women aged 65 years or older
* All women aged 60 to 64 years with
– Family history of fragility fracture
– Body weight <70 kg
– Prior nontraumatic fracture
– Other risk factors
* Postmenopausal women of any age receiving aromatase inhibitors
* Premenopausal women with therapy-associated premature menopause
Repeat BMD annually after initial examination.
Bisphosphonates are divided into 2 classes based on their chemical structure and mechanism of action—
nitrogen-containing bisphosphonates (ie, alendronate, ibandronate, pamidronate, risedronate, zoledronic
acid) and non–nitrogen-containing bisphosphonates (ie, clodronate, etidronate).[92] Nitrogen-containing
bisphosphonates are more potent than non–nitrogen-containing bisphosphonates because they inhibit the
enzyme farnesyl diphosphate synthase, an enzyme in the cholesterol biosynthesis pathway.
During bone formation, the biochemical markers released into the circulation include bone-specific ALP,
the procollagen extension peptides (PICP, PINP), and OC.[7,68] ALP and OC are measured in serum. Bone
resorption leads to collagen breakdown and results in the release of bone resorption markers into the
circulation, including NTx, CTx, Pyr, and DPD.
Commonly used radiopharmaceuticals include strontium chloride-89, sodium phosphate-32, and samarium-153
lexidronam. In patients with bone metastases, radiopharmaceuticals may be used as an alternative or
adjunct to external beam radiation therapy.[84,85] These agents are not useful in spinal cord or
peripheral nerve invasion by adjacent metastases, for acute pathologic fractures, or for pure osteolytic
lesions.
Table 4. Proposed Scoring System for Predicting Risk of Pathologic Fracture Through a Metastatic Lesion in
a Long Bone. Reprinted with permission from Mirels H et al. Clin Orthop Relat Res. 1989;249:256-265.
Points
1 2 3
Image Blastic Mixed Lytic
Size <1/3 1/3 to 2/3 >2/3
Site Upper extremity Lower extremity Peritrochanteric
Pain Mild Moderate Mechanical
This system grades each of 4 radiographic and clinical risk factors on a scale of 1 to 3. The authors
suggest that lesions with a cumulative score of 7 or less can be safely irradiated without risk of
fracture, while a score of 8 or higher (higher risk of fracture) should prompt prophylactic internal
fixation prior to irradiation.
Disease-free and overall survival were significantly better with clodronate. With longer follow-up (103 ±
12 months), the incidence of osseous and visceral metastases was similar in both groups.[103] A difference
in disease-free survival could no longer be demonstrated; however, overall survival was still
significantly better with clodronate (P < .01). The authors concluded that adjuvant clodronate therapy
prolongs survival in patients with breast cancer.[103]=# Jaschke A, Bastert G, Solomayer EF, et al.
Adjuvant clodronate treatment improves the overall survival of primary breast cancer patients with
micrometastases to bone marrow—a longtime follow-up. Proc Am Soc Clin Oncol. 2004;23:9. Abstract 529.
Osteonecrosis of the jaw (ONJ) is a serious dental condition that has been reported inpatients receiving
IV and, to a lesser extent, oral bisphosphonates.114,115 Incidence has been reported in a recent large,
retrospective review series at 0.6%.[116]=Van Poznak CH, Estilo CL, Sauter NP, et al. Osteonecrosis of the
jaw in patients with metastic breast cancer. Presented at 27th Annual Breast Cancer Symposium; December 9,
2004; San Antonio, Tex. Abstract 3057.
Medscape
Posted by: Ds20040999 / 6:55 PM 
