Early diagnosis of heterotopic ossification among patients admitted to a neurological Post-Intensive Care Rehabilitation Unit.

BACKGROUND: Heterotopic ossification (HO) is defined as the formation of endochondral bone within soft tissue. Non-genetic forms, mainly corresponding to a consequence of bone, brain or spinal cord injury, are the most common. HO leads to important functional limitations and alteration of quality of life. To our knowledge, the time between brain, bone, or spinal cord injury and clinical suspicion of HO has never been studied. By admitting patients with severe neurological disorders, we hypothesized that the prevalence of HO in neurological post-intensive care rehabilitation units (PICRU) might be significant as these patients have recognized risk factors for HO. AIM: This study aimed to investigate HO among patients admitted to a neurological PICRU with two objectives: 1) to describe the prevalence of HO in PICRU; 2) to assess the time between neurological disorder, clinical suspicion of HO and radiological diagnosis. DESIGN: A monocentric retrospective cohort study. SETTING: PICRU in our public university teaching hospital. This inpatient referral department is specifically dedicated to the early discharge from Intensive Care Units (ICU) of patients with severe neurological impairment who need rehabilitation. POPULATION: We study all patients admitted between April 2016 and January 2019. One hundred twenty-five subjects were admitted for a rehabilitation program after neuro-trauma or stroke. We included all first-time stays in PICRU lasting 7 days or longer. METHODS: Retrospective data extraction using administrative data from an electronic patient management program was done to select eligible subjects. Included subjects were then identified by a retrospective review of electronic inpatient medical records after patient discharge. Data of interest were collected from these same medical records. RESULTS: Forty-four HO were diagnosed in 24 subjects (24/125; 19%), with a median number of 2 [1; 2] HO per subject. Neurological trauma was the main reason for admission to ICU (89/125; 71%) and half of patients had a traumatic brain injury (TBI) (67/125; 54%). The diagnosis of HO was made in PICRU in 75% of cases. Clinical suspicion of HO (autonomic dysfunction, local inflammatory signs, pain, or reduced joint range of motion) was made 6 [5; 7] weeks after admission to ICU. Radiological confirmation of clinical suspicion or fortuitous diagnosis by imaging (50% of the cases) occurred 8 [7; 12] weeks after admission to ICU. The median time of clinical suspicion or radiological diagnosis was 1 week after admission to PICRU. CONCLUSIONS: HO is a sub-acute complication which develops in patients admitted to ICU for severe central nervous system disorders as clinical suspicion or radiological confirmation of diagnosis was made within the first week after admission in neurological PICRU (i.e. 6 to 8 weeks after ICU admission). CLINICAL REHABILITATION IMPACT: As treatment for HO may at least partially improves rehabilitation and quality of life, we recommend a systematic screening in PICRU patients for HO by clinical examination supplemented by imaging in case of suspicion.

Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression.

Lactation induces bone loss to provide sufficient calcium in the milk, a process that involves osteoclastic bone resorption but also osteocytes and perilacunar resorption. The exact mechanisms by which osteocytes contribute to bone loss remain elusive. Osteocytes express genes required in osteoclasts for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression. We show that Ctsk deletion in osteocytes prevented the increase in osteocyte lacunar area seen during lactation, as well as the effects of lactation to increase osteoclast numbers and decrease trabecular bone volume, cortical thickness and mechanical properties. In addition, Ctsk deletion in osteocytes increased bone Parathyroid Hormone related Peptide (PTHrP), prevented the decrease in serum Parathyroid Hormone (PTH) induced by lactation, but amplified the increase in serum 1,25(OH)2D. The net result of these changes is to maintain serum and milk calcium levels in the normal range, ensuring normal offspring skeletal development. Our studies confirm the fundamental role of osteocytic perilacunar remodeling in physiological states of lactation and provides genetic evidence that osteocyte-derived Ctsk contributes not only to osteocyte perilacunar remodeling, but also to the regulation of PTH, PTHrP, 1,25-Dyhydroxyvitamin D (1,25(OH)2D), osteoclastogenesis and bone loss in response to the high calcium demand associated with lactation.

Increased proportion of hypermineralized osteocyte lacunae in osteoporotic and osteoarthritic human trabecular bone: implications for bone remodeling.

Hypermineralized osteocyte lacunae (micropetrosis) have received little research attention. While they are a known aspect of the aging human skeleton, no data are available for pathological bone. In this study, intertrochanteric trabecular bone cores were obtained from patients at surgery for osteoporotic (OP) femoral neck fracture (10F, 4M, 65-94 years), for hip osteoarthritis (OA; 7F, 8M, 62-87 years), and femora at autopsy (CTL; 5F, 11M, 60-84 years). Vertebral trabecular bone cores were also obtained from the vertebra of autopsy cases (CVB; 3F, 6M, 53-83 years). Specimens were resin-embedded, polished, and carbon coated for quantitative backscattered electron imaging (qBEI), energy dispersive X-ray (EDX) spectrometry, and imaging analysis. Bone mineralization (Wt %Ca) was not different between OP, OA, and CTL; but was greater in femoral CTL than in CVB. The percent of hypermineralized osteocyte lacunae relative to the total number (HL/TL) was greater in OP and OA than in CTL. However, relative to bone mineral area, OP was characterised by increased hypermineralized osteocyte lacunar number density (Hd.Lc.Dn), whereas OA was characterised by decreased osteocyte lacunar number density (Lc.Dn) and total osteocyte lacunar number density (Tt.Lc.Dn). Lc.Dn was higher in CVB than in femoral CTL. The calcium-phosphorus ratio (R(Ca/P)) was not different between hypermineralized osteocyte lacunae and bone matrix in each group. In addition, this study focused on the phenomenon of osteocyte lacunae hypermineralization using qBEI. Seven morphological types of osteocyte lacunae hypermineralization were described according to the presence of one or several hypermineralized spherites, associated or not with a hypermineralized lacunar ring. This study has described, for the first time, the morphology of hypermineralized osteocyte lacunae in OP and OA human bone. Further studies are suggested to investigate the functional influence of hypermineralized osteocyte lacunae on bone remodeling and bone biomechanical properties.