Bone scan

Bone scintigraphy should not be used to detect myeloma bone lesions. Its sensitivity is low because osteoblast activity is suppressed and no radionuclide (99 Technetium-diphosphate) is taken up.

Increased activity in the ribs in a pattern suggesting healing rib fractures (my personal archive):


Example of bone scintigraphy in MM (my personal archive):



False negative results - a patient with multiple myeloma had several active bone lesions, but bone scan failed to identify most of them (my personal archive):



Comparison between PET scan (left side) and bone scan (right side) in the same patient (my personal archive). Many myelomatous lesions in the bones are invisible in the bone scan.






See specific section.





See specific section.






In MM, the technetium-99m-2-methoxy-isobutyl-isonitrile (Tc99m-sestaMIBI) scan has an inferior value compared to the PET scan.

Detection of focal myeloma lesions by technetium-99m-sestaMIBI scintigraphy.
Haematologica. 1999 Feb;84(2):119-24.
Catalano L, Pace L, Califano C, Pinto AM, De Renzo A, Di Gennaro F, Del Vecchio S, Fonti R, Salvatore M, Rotoli B.
This study evaluates the role of Tc99m-sestaMIBI scan in the diagnosis of focal myeloma lesions in 55 patients with MM, solitary plasmacytoma, or MGUS. The authors found that, in untreated patients, the number of lesions revealed by the sestaMIBI scan was similar to that seen at conventional radiographs. Instead, in pretreated patients, the sestaMIBI scvan revelaed a lower number of lesions lower, because sestaMIBI traced only the active lesions. The sestaMIBI scan cannot easily detect small focal lesions, especially those <1 cm in size. The sestaMIBI scan is more specific than conventional radiographs in identifying sites of active disease.

99mTc-MIBI scintigraphy in untreated stage III multiple myeloma: comparison with X-ray skeletal survey and bone scintigraphy.
Nucl Med Commun. 2003 May;24(5):537-42.
Alper E, Gurel M, Evrensel T, Ozkocaman V, Akbunar T, Demiray M.
This study evaluated the role of the 99mTc-MIBI scan, compared with skeletal survey and bone scintigraphy, in the disease assessment of 20 patients with advanced stage MM. The authors found that the 99mTc-MIBI scan is a very sensitive imaging modality for the identification of active disease in patients with advanced MM, and it can detect sites of disease that are sometimes missed by the skeletal survey and the bone scintigraphy.

Comparison of Technetium-99m-MIBI imaging with MRI for detection of spine involvement in patients with multiple myeloma.
BMC Nucl Med. 2003 Dec 11;3(1):2.
Mirzaei S, Filipits M, Keck A, Bergmayer W, Knoll P, Koehn H, Ludwig H, Pecherstorfer M.
This study compared Tc-99m-MIBI scan and MRI in the detection of myelomatous bone lesions. The authors found that the Tc-99m-MIBI scan underestimates the extent of myelomatous bone marrow infiltration in the spine, especially in patients with low disease stage. Among 21 patients with MM, the Tc-99m-MIBI scan missed bone marrow involvement in 43 of 87 vertebrae (50.5%) in which the MRI showed bone marrow infiltration. In patients with low disease stage (stage I and II), the Tc-99m-MIBI scan was negative in all of 24 vertebrae infiltrated according to the MRI findings.

Baseline Tc99-MIBI scanning predicts survival in multiple myeloma and helps to differentiate this disease from monoclonal gammopathy of unknown significance.
Haematologica. 2005 Aug;90(8):1141-3.
Martín MG, Romero Colás MS, Dourdil Sahún MV, Olave P, Alba PR, Banzo JB.
These authors obtained baselineTc(99)-MIBI scanning in 43 patients with multiple myeloma and in 31 with MGUS, and they found a correlation between results and patients' survival.

Tc99m-sestaMIBI uptake in nonsecretory multiple myeloma.
Hematology. 2005 Aug;10(4):335-8.
Catalano L, Andretta C, Pace L, Del Vecchio S, Salvatore B, De Rosa G, Buonanno MT, Paone G, Rotoli B.
These authors evaluated the role of Tc99m-sestaMIBI scintigraphy at diagnosis and follow-up of 9 patients with non-seccretory myeloma. They found that Tc99m-sestaMIBI scintigraphy has a high sensitivity (no false positive cases) and 78% specificity (2 of 9 cases were false negative). They advocate a role for this imaging modality in the monitoring of non-secretory myeloma, and they conclude that it should be considered complementary to conventional imaging studies.




Biochemical markers


Markers of osteoblastic activity:
 - Bone-specific alkaline phosphatase
   Serum alkaline phosphatase is elevated in only 30% of MM patients
 - Osteocalcin
Markers of osteoclastic activity:
 - Pyridinolines and deoxypyridinolines in urine
 - Cross-linked aminoterminal telopeptide of type I collagen (NTx) in serum and urine
 - Carboxy terminal telopeptide of type I collagen (ICTP) in serum
   It is a breakdown product of type I collagen and it comprises 90% or more of organic substances in bone


Evaluation of bone disease in multiple myeloma: a correlation between biochemical markers of bone metabolism and other clinical parameters in untreated multiple myeloma patients.
Clin Chim Acta. 2002 Nov;325(1-2):51-7.
Alexandrakis MG, Passam FH, Malliaraki N, Katachanakis C, Kyriakou DS, Margioris AN.
These authors studied several biochemical markers in MM, including osteocalcin, bone-specific alkaline phosphatase, free urine pyridoline and deoxypyridinoline, and free urine NTx in 38 patients with newly diagnosed MM, and correlated their findings with the degree of bone involvement at the skeletal survey. They found that levels of NTx, free urine pyridoline, and free urine deoxypyridinoline increased with increasing degree of bone involvement. Instead, osteocalcin levels were increased in stages I and II of MM compared to stage III.

Urinary N-telopeptide levels in multiple myeloma patients, correlation with Tc-99m-sestaMIBI scintigraphy and other biochemical markers of disease activity.
Hematol Oncol. 2003 Mar;21(1):17-24.
Alexandrakis MG, Kyriakou DS, Passam FH, Malliaraki N, Vlachonikolis IG, Karkavitsas N.
Urinary cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a sensitive and specific marker of bone resorption in multiple myeloma (MM). These authors have measured the levels of cross-linked N-telopeptide of type I collagen (NTx) in the urine of 30 newly diagnosed MM patients and 25 controls and tehy correlated the levels with the degree of bone involvementt seen at the Tc-99m-MIBI scintigraphy, Durie-Salmon stage, and bone marrow infiltration by plasma cells. The NTx was found at significantly higher concentrations in patients with greater bone involvement at Tc-99m-sestaMIBI and higher bone marrow infiltration. The authors conclude that NTx is a useful marker for monitoring bone resorption in MM.

Prognostic value of urinary pyridinium crosslinks and their derivatives in multiple myeloma.
Ann Hematol. 2005 Jan;84(1):19-24.
Samani KK, Brazier M, Mathiot C, Kamel S, Jamart J, Jaubert J, Blanc M, Azaïs I, Facon T, Leleu X.



Giampaolo Talamo, M.D.