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PubMed1982

[Dichloromethylene diphosphonate (Cl2MDP) treatment of hypercalcaemia produced from bone metastases (author's transl)].

Cl2MDP, a potent inhibitor of osteoclast-mediated bone resorption, was tested in 8 patients with malignant hypercalcaemia. In a 2 months' double-blind, cross-over study the patients received Cl2MDP (3200 mg/day) during 4 weeks and a placebo during 4 weeks in a randomized sequence. The serum Ca level fell from a mean pre-trial value of 12.2 +/- 1.7 mg/dl to 10.3 +/- 1.4 mg/dl after 4 weeks of Cl2MDP (p = 0.01). Reduction was rapid, with a mean serum Ca value of 10.5 +/- 1.4 mg/dl as early as the 3rd day. At the end of the Cl2MDP treatment, 6 out of the 8 patients had normal serum Ca levels. Following active treatment, the serum Ca level significantly increased in 2 patients and remained low in one patient under placebo. Treatment with Cl2MDP resulted in a decrease in calciuria from 397 +/- 193 mg/g creatinine/24 hours to 241 +/- 211 mg/g creatinine/24 hours (p = 0.05), but there was no decrease in hydroxyproline. Serum phosphorus and PTH levels remained normal. It is concluded that Cl2MDP is an effective and convenient oral treatment of hypercalcaemia due to bone metastases.

Adult↗
PubMed1982

A technique to evaluate bone healing in non-human primates using sequential 99mTc-methylene diphosphonate scintigraphy.

The assessment of bone healing through sequential nuclear medical scintigraphy requires a method of consistent localization of the exact fracture area in each consecutive image as the study progresses. This is difficult when there is surrounding bone activity as in the early stages of trauma, and also if complications should set in. The image profile feature, available from most nuclear medical computer software, facilitates this procedure considerably, as is indicated in the present report on bone healing in baboons. Together with roentgenology and histology a 99mTc-MDP study was in this way successfully done on the healing of long bone fractures experimentally induced in non-human primates. Different surgical implants were used. The results indicate that 99mTc-MDP accurately reflects the physiological activity in bone. The time-activity curves obtained are presently being studied together with extensive histology, bearing possible clinical application in mind.

Animals↗
PubMed1983

Sustained biochemical effects of short treatment of Paget's disease of bone with dichloromethylene diphosphonate.

The relationship between duration of treatment and biochemical parameters reflecting antiosteoclastic activity was studied in 26 patients with Paget's disease of bone receiving Cl2MDP 1600 mg/day. Six months after initiation of therapy, the reduction in total urinary hydroxyproline was not different in patients treated for 1, 3, 5, or 6 months. This remission lasted 1 year for all groups. In contrast, the longest treatment induced the greatest reduction in serum alkaline phosphatase. One year after the initiation of therapy, this reduction was sustained, whereas a slight relapse was noted in other groups. From these findings, it appears that a rapid bone load with oral Cl2MDP can induce a long-lasting reduction in bone resorption excess.

Adult↗
PubMed1983

Lack of a T-cell dependent subpopulation of macrophages in (dichloromethylene) diphosphonate-treated mice.

In Cl2MDP-osteopetrotic mice, one subpopulation of thioglycollate-induced peritoneal exudate macrophages (M phi) is missing. This subpopulation is precisely the one whose differentiation is known to be dependent on T-lymphocytes, as it is also missing in the athymic nu/nu mice. Cl2MDP-induced osteopetrosis being partially attributable to deficient osteoclastic bone resorption, raises the possibility that this missing M phi subpopulation might represent the precursors of osteoclasts. It is suggested from this work that the interplays between T-cells and M phi, so well known in immunity and inflammation, may also be relevant to osteoclastic differentiation and therefore, to bone remodeling.

Animals↗
PubMed1984

Calcification and uptake of Tc-99m diphosphonates in neuroblastomas: concise communication.

Sixty-six percent of 54 patients with neuroblastoma demonstrated uptake of bone-seeking radioagents by the primary tumor. This is a higher incidence than previously reported. Uptake was slightly more common in abdominal than thoracic tumors. There was a significant correlation between the size of the tumor and tracer uptake. Calcification was demonstrated in the primary tumor in almost 90% of the 54 patients. This is a much higher incidence of calcification than previously reported. Microscopy shows that the calcification is not always due to tumor necrosis; it also occurs in areas of viable tumor cells. Tracer uptake is believed to be related to calcium metabolism. The rate of metabolic activity rather than the total amount of calcium present within the tumor may be the most important factor in determining the amount of uptake. No significant relationship was found between tracer uptake and tumor stage or homovanillic acid and vanillylmandelic acid metabolic activity.

Abdominal Neoplasms↗