Histomorphometric evaluation of daily and intermittent oral ibandronate in women with postmenopausal osteoporosis: results from the BONE study

Abstract

The bisphosphonate ibandronate, administered either daily or intermittently with an extended between-dose interval of >2 months, has been shown to reduce significantly the incidence of vertebral fractures, to increase bone mineral density and to reduce levels of biochemical markers of bone turnover in a phase III randomized study in women with postmenopausal osteoporosis (PMO). Bone histomorphometry was performed on a subgroup of women participating in this study in order to assess bone quality and architecture. The patients were randomized to receive one of the following: placebo, continuous oral daily ibandronate (2.5 mg/day) or intermittent oral ibandronate (20 mg every other day for 12 doses every 3 months). Out of the overall study population of 2,946 patients, 110 were randomly assigned to undergo transiliac bone biopsy at either month 22 or month 34 of treatment. The primary safety endpoint was osteoid thickness in trabecular bone, which was measured to exclude treatment-induced bone mineralization defects. Secondary safety endpoints assessed bone volume, bone turnover and micro-architecture. The primary efficacy endpoint was bone mineralizing surface. In all bone biopsy cores, newly formed trabecular bone retained its structure without any signs of woven bone. Marrow fibrosis and signs of cellular toxicity were not observed. Quantitative assessment demonstrated no impairment in mineralization of bone matrix: osteoid thickness tended to be similar or slightly lower in the ibandronate groups versus the placebo group. All secondary safety variables and the bone efficacy parameter were consistent with the production of normal-quality, newly formed bone and a modest reduction in bone turnover with both ibandronate regimens relative to placebo. Long-term treatment with oral ibandronate, even when administered with an extended between-dose interval of >2 months, produces normal-quality, newly formed bone in women with PMO.

Bisphosphonate effects on bone turnover, microdamage, and mechanical properties: What we think we know and what we know that we don't know

“…These studies consistently show alendronate suppresses remodeling more than risedronate [8,9] while zoledronate suppresses more than risedronate [10]. No head-tohead assessments of bone remodeling among the BPs has been conducted using histology as an outcome, yet based on iliac crest biopsy studies from the major clinical trials the percent suppression of remodeling relative to placebo-treated controls tends to be quite similar over 3 years with daily risedronate (-40%) [11], daily alendronate (-92%) [12], intermittent oral ibandronate (-50%) [13], and zoledronate (-63%) [14].…”

Bone quality: what is it and how is it measured?

“…Antiresorptive agents preserve existing bone architecture, as demonstrated in iliac crest biopsies using 2-dimensional histological techniques in women treated with hormone replacement therapy (34), raloxifene (29) or ibandronate (26) and µCT in women treated with risedronate (35,36). Decreased cortical porosity (37) and unchanged cortical thickness (35) have also been reported in iliac crest bone obtained from women undergoing treatment with anti-resorptive therapy.…”

“…The most potent effects are seen with alendronate, zoledronate and ibandronate, which reduce activation frequency in iliac crest bone biopsies by around 75-90% (24)(25)(26). Risedronate and hormone replacement therapy are of intermediate potency, with a reduction of around 50% (27,28) and the smallest effect is seen with raloxifene (approximately 20%) (29).…”

The qualitative evaluation of the jaw bones in the patients undergoing combined anti-osteoporotic therapy

“…В литературе описаны случаи остеонекроза че-люстных костей у пациентов, получавших терапию бисфосфонатами, частота встречаемости которого, по некоторым данным, составляет от 6,5 до 12,5% [8][9][10].…”

“…Одни авторы связывают его возникновение с дисбалан-сом процессов костного ремоделирования, усилен-ным образованием провоспалительных цитокинов, наличием патогенной микрофлоры в полости рта [8,9], другие считают, что при длительном применении бисфосфонаты блокируют функцию остеобластов путем прямого ингибирования активности остео-кластов [10].…”