The influence of calcium channel blockers on Ca−P−Mg homeostasis and bone mass in patients with coronary heart disease and hypertension

Abstract

Calcium channel blockers (Ca-B) modify L-type .channels, decreasing the number ofintracellular calcium ions. In consequence contractility of muscle cells, enzymes excretion and hormones production are beeing modified. L-type calcium channels have been found in osteoblasts therefore Ca-B cotdd be expected I0 influence bone cells remodelling activity. The purpose of th:e study was to evaluate whether Ca-B ar e able to modify Ca-P-Mg homeostasis and influence bone mass.9 . . . . : ~ . Twenty two patients, aged 51 _+9, were treated for 2 years with nifedipine in a dose of 30 mg daily, due to coronary heart disease and/or hypertension. The group of twenty age matched volunteers served as the controls. Prior to the treatment and than in 6-month intervals serum levels of calcium, inorganic phosphate, magnesium and alkaline phosphatase activity as well as fasting urine calcium ereatinine ratio were determined. Bone mineral density (BMD) of the lumbar spine and proximal femur were measured with the method of dual energy X-ray absorptiometry (DXA). Conventional X-ray examinations of thoracic and lumbar spine were performed.It was found that 24-month treatment with nifedipine increased serum calcium and inorganic phosphate concentrations with no influence on bone turnover markers. Apart from temporary increase of BMD in the femoral neck, in 6th and 12th months of the study, no significant changes in bone mass were observed. Deoxypyridinoline (Dpd) is a nonreducible crosslink of type I collagen in bone which provides rigidity and strength. The Dpd crosslink is released into circulation as a result of osteoclastic degradation of bone, is excreted unmetabolized in urine, and is unaffected by diet. Increased levels of Dpd have been reported in patients at risk of bone loss (postmenopausal women and patients with metabolic bone disorders such as osteoporosis and Paget's disease of bone) and levels have been reported to return to normal in response to antiresorptive therapy. The Pyrilinks*-D enzyme immunoassay (EIA) for the measurement of Dpd has been shown to be a sensitive and reproducible indicator of bone resorption (Robins et al. J Bone Miner Res 1994;9:1643-1649, and to reflect changes in resorption after treatment with various antiresorptive drugs. We have developed a coated tube RIA for the measurement of Dpd in urine utilizing the anti-Dpd monoclonal antibody from the Pyrilinks-D EIA. This antibody has selective high affinity for free Dpd and exhibits low cross-reactivity to pyridinoline (Pyd; < 1%) and Pyd-or Dpd-containing peptides (<2.5%). In the RIA, the anti-Dpd antibody is coated on the tube and purified Dpd is labeled with 125I. The Dpd in the sample and the labeled Dpd compete for the antibody coated on the tube. The unbound Dpd is washed away and the tubes are counted in a gamma counter. Preliminary evaluation of this new RIA revealed the following results: correlation to the Pyrilinks-D EIA r2=.97, m=.98; linearity average 99.4%; spike recovery average 94.7%; intra-and inter-assay precision average CVs 3.4 and ...

Long-term effects of antihypertensive medications on bone mineral density in men older than 55 years

“…Kapitan-Malinowska et al report that calcium channel blocker treatment increases serum calcium and inorganic phosphate concentrations but has no effect on bone turnover markers or BMD. 26 In a study investigating whether amlodipine interferes with healing of rat alveolar bone, a 20-30% decrease in bone volume fraction in the alveolus of amlodipine-treated animals was reported, which may be a sign of decreased osteoblastic activity. 27 Takaoka et al maintained that calcium channel blocker treatment significantly increases fracture risks after adjustments for age, body mass index, serum creatinine, and blood pressure levels in patients with type 2 diabetes mellitus.…”

ASM Sci. J., Vol. 3, No. 1, 2009

“…The drug exhibited an inhibitory effect on bone resorption by causing a direct influx of calcium into the cells ( Ritchie et al 1994) . Clinically, it has been reported that elderly patients treated for coronary heart disease over two years, Nifedipine caused a temporary increase in bone minerals density (Malinowska et al 1996). In the combination group, subsequent bone resorption and deposition or remodeling caused the obvious appearance of the incremental lines (Poliana et al 2001).…”

Short-term immunosuppressive therapy does not affect the density of the pre-existing bone around titanium implants placed in rabbits

“…Osteoclast activity depends upon calcium concentration, and CCBs can lead to a rapid increase of cytosolic free calcium with effects on osteoclast morphology and a marked dose-dependent fall in the cell spread area and osteoclast bone resorption 29 . Clinically, it has been reported that, in elderly patients treated for coronary heart disease over 2 years, nifedipine caused a temporary increase in bone mineral density 18 .…”