The many facets of micropetrosis - Magnesium whitlockite deposition in bisphosphonate-exposed human alveolar bone with osteolytic metastasis.

Abstract

The lacuno-canalicular space of apoptotic osteocytes eventually becomes mineralised in vivo. This condition is known as micropetrosis and is a fundamental characteristic of ageing bone. Increased prevalence of such hypermineralised osteocyte lacunae is viewed as a structural marker of impaired bone function - both mechanical and biological. Within the lacuno-canalicular space, mineralised apoptotic debris typically occurs as micrometre-sized, spherical nodules of magnesium-rich, carbonated apatite. Moreover, characteristically facetted, rhomboidal nodules of magnesium whitlockite [Mg-whitlockite; Ca18Mg2(HPO4)2(PO4)12] have been reported in human alveolar bone exposed to the bisphosphonate alendronate. This work provides supporting evidence for Mg-whitlockite formation in the alveolar bone of a 70-year-old male exposed to the bisphosphonate zoledronic acid to suppress osteolytic changes in skeletal metastasis. Backscattered electron scanning electron microscopy (BSE-SEM) revealed spherical and rhomboidal nodules within the lacuno-canalicular space. A variant of spherical nodules exhibited a fuzzy surface layer comprising radially extending acicular crystallites. The rhomboidal nodules ranged between ∼200nm to ∼2.4µm across the widest dimension (652±331nm). Micro-Raman spectroscopy and energy dispersive X-ray spectroscopy confirmed that rhomboidal nodules are compositionally distinct from spherical nodules, exhibiting higher Mg content and lower Ca/P ratio. Formation of Mg-whitlockite within osteocyte lacunae is multifactorial in nature and suggests altered bone biomineralisation. Nevertheless, the underlying mechanism(s) and sequence of events remain poorly understood and warrant further investigation. The possibility to discriminate between carbonated apatite and Mg-whitlockite nodules within osteocyte lacunae, based on particle morphology, attests to the diagnostic potential of BSE-SEM with or without additional analyses of material composition.