Focal mineralization defect during disodium etidronate treatment of calcinosis

Abstract

The use of disodium etidronate (EHDP) for the treatment of calcinosis is complicated by the threat of drug-induced inhibition of skeletal mineralization. Adults with Paget's disease of bone treated for 6 months with 10-20 mg/kg/day of EHDP have been reported to show both a marked delay in mineralization and a diffuse excess of unmineralized bone matrix. Drug-induced bone disease is, however, a function of growth as well as of the dose and duration of therapy. Therefore, children treated with EHDP may respond differently to the drug-induced mineralization defect. A 10-year-old girl with dermatomyositis developed incapacitating ectopic calcification. After 9 months of therapy with 12 mg/kg/Day of EHDP, a small decrease in the calcinosis was accompanied by a dramatic increase in joint mobility. Bone mineral content of the radial diaphysis showed a failure to gain mineral density as expected with prepubertal growth (8 cm/year). Bone biopsy revealed a patchy excess of osteoid. Although the percentage of osteoid surface labeled by tetracycline was reduced, normal mineralization was evident in the double-labeled areas. In children, the mineralization defect occurring with EHDP treatment may be focal.

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

“…After 3 years of treatment, 55 patients volunteered to undergo a transiliac bone biopsy to determine whether the drug had impaired skeletal mineralization, as had occurred with etidronate, a first-generation bisphosphonate 17. To label the bone for the measurement of the mineral appositional rate and the mineralizing perimeter, the patients were given oral tetracycline hydrochloride (250 mg four times per day) 19, 18, 7, and 6 days before the biopsy.…”

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

“…[1][2][3] After 3 years of treatment, 55 patients volunteered to undergo a transiliac bone biopsy to determine whether the drug had impaired skeletal mineralization, as had occurred with etidronate, a first-generation bisphosphonate. 17 To label the bone for the measurement of the mineral appositional rate and the mineralizing perimeter, the patients were given oral tetracycline hydrochloride (250 mg four times per day) 19, 18, 7, and 6 days before the biopsy. Thus, each patient underwent two periods of tetracycline labeling separated by an interval of approximately 2 weeks.…”

“…13,17,18,21 The total number of osteoclasts on or adjacent to cancellous bone was expressed as the number per millimeter of cancellous bone perimeter. A giant osteoclast was defined as one having at least three of the following characteristics: more than eight nuclear profiles (two-dimensional images of a section taken through three-dimensional objects), detachment from bone, a shallow or absent resorption cavity, pyknotic nuclei, or the presence of other mononuclear cells interposed between the bone perimeter and the osteoclast.…”

Uso do clodronato endovenoso na calcinose difusa em uma criança com síndrome de superposição esclerose sistêmica e dermatomiosite

“…Várias drogas têm sido testadas, como a probenecida (5,6) , o warfarin (7,8) , o diltiazem (9,10) , o hidróxido de alumínio (11,12) , e a colchicina (13) , mas nenhuma delas demonstrou resultados consistentes. Há poucos dados sobre o uso dos bisfosfonatos na calcinose cutânea (4,14,15) . A razão para o seu uso reside na hipótese de que parte do cálcio presente nas calcificações seja originada do osso, e na elevada remodelação óssea presente em alguns destes pacientes (3) ; desta forma, a inibição da reabsorção óssea diminuiria a disponibilidade de cálcio, reduzindo sua deposição nos nódulos calcificados.…”