Binding of the bone-seeking agent99mTc-1-hydroxyethylidene-1,1-diphosphonic acid to cartilage and collagen in vitro and its stimulation by Er3+ and low pH

Abstract

The bone-seeking agent 99mTc-labeled 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) unexpectedly binds to particles of human articular cartilage as well as cortical bone in vitro. Collagen also sequesters this compound, suggesting that collagen contributes to the uptake of 99mTc-HEDP by cartilage and bone. Particles of the bone mineral calcium hydroxyapatite also bind 99mTc-HEDP in vitro. Pretreatment of particles with Er3+ stimulates binding in each case. Lowering the pH of incubation to pH 2 has this effect for bone, cartilage, and collagen, but not for calcium hydroxyapatite. Mechanisms additional to the simple ionic attraction between the phosphonate groups of HEDP and metal cations such as Ca2+ are responsible for the uptake of 99mTc-HEDP by body tissues.

The promotion of collagen polymerization by lanthanide and calcium ions

“…Ions of the lanthanide series (Ln3+), which often serve as isomorphous replacements for Ca2+ in biochemical systems (Williams, 1979), have also been used. That Ln3+ might prove useful in the present context is suggested by previous work from this laboratory (Evans & Mears, 1980;Evans & Tew, 1981;Evans, 1981).…”

Bisphosphonates for osteoarthritis prevention: "Holy Grail" or not?

“…Also of potential benefit in OA, bisphosphonates have effects beyond the osteoclast and may be slightly immunomodulating via inhibition of pro-inflammatory cytokines 2. In vitro, etidronate binds to human cartilage3 and can modestly inhibit matrix metalloproteinases 4. Neridronate stimulated osteoblasts to produce osteocalcin in an OA model, providing yet another potential pathway for bisphosphonate activity in OA 5.…”

Bone marrow lesions in the knee: the clinical conundrum

“…Previous histological studies 4,5,7 have confirmed the presence of increased osteoclastic activity with lymphocytic and plasma cell infiltration, which points to the use of bisphosphonates, as they have been found to exert slight immunomodulating effects by inhibiting pro‐inflammatory cytokines 34 . In vitro , bisphosphonates can bind to cartilage 35 and slightly inhibit matrix metalloproteinases 16 . In clinical trials examining the efficacy of bisphosphonates in OA, alendronate reduced MRI‐observed BMLs in a cohort of women but did not halt radiological progression 18 .…”