Osteoblast Recruitment Routes in Human Cancellous Bone Remodeling

It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling is lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels on these respective surfaces, and that bone formation occurs only above a given cell density. Canopies appeared an important source of osteoprogenitors, because (i) canopy cells proved to be more proliferative and less differentiated than bone surface cells, as shown by the inverse levels of Ki-67 and procollagen-3 N-terminal peptide versus osterix, and (ii) canopy cell densities, found to decline with age, and canopy-capillary contacts above eroded surfaces correlated positively with osteoblast density on bone-forming surfaces. Furthermore, we showed that bone remodeling compartment canopies arise from a mesenchymal envelope surrounding the red bone marrow, which is lifted and hypertrophied on initiation of bone resorption. This study, together with earlier reports, led to a model in which canopies and nearby capillaries are critical for reaching the osteoblast density required for bone formation

Total thyroidectomy: reduction in postoperative hypoparathyroidism

Objective: Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy oper ations for Graves’ disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves’ disease. Design: Retrospective cohort study from a single institution. Methods: We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves’ disease. Results: We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012–2014 to 6% in 2020–2021. For patients with Graves’ disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015–2016 to 2% (1 out of 56) in 2020–2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012–2014 to 10% (10 out of 51) in 2020–2021. Conclusion: Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery. Significance statement: Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoper ative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves’ disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures

Innervation is higher above Bone Remodeling Surfaces and in Cortical Pores in Human Bone:Lessons from patients with primary hyperparathyroidism

Abstract Mounting evidence from animal studies suggests a role of the nervous system in bone physiology. However, little is known about the nerve fiber localization to human bone compartments and bone surface events. This study reveals the density and distribution of nerves in human bone and the association of nerve profiles to bone remodeling events and vascular structures in iliac crest biopsies isolated from patients diagnosed with primary hyperparathyroidism (PHPT). Bone sections were sequentially double-immunostained for tyrosine hydroxylase (TH), a marker for sympathetic nerves, followed by protein gene product 9.5 (PGP9.5), a pan-neuronal marker, or double-immunostained for either PGP9.5 or TH in combination with CD34, an endothelial marker. In the bone marrow, the nerve profile density was significantly higher above remodeling surfaces as compared to quiescent bone surfaces. Ninety-five percentages of all nerve profiles were associated with vascular structures with the highest association to capillaries and arterioles. Moreover, vasculature with innervation was denser above bone remodeling surfaces. Finally, the nerve profiles density was 5-fold higher in the intracortical pores compared to bone marrow and periosteum. In conclusion, the study shows an anatomical link between innervation and bone remodeling in human bone

Hypoparathyroidism following total thyroidectomy: high rates at a low-volume, non-parathyroid institution

BackgroundHypoparathyroidism following total thyroidectomy is globally the most common complication to thyroid surgery. The reported complication rates vary widely and might be highly dependent on the surgical experience. In this study we aimed to evaluate the rate of hypoparathyroidism following primary total thyroidectomy at a low-volume institution that only performs thyroid surgery and does not have any experience with parathyroid surgery.MethodsRetrospective cohort study. All patients undergoing primary total thyroidectomy at the ENT-Department, Goedstrup Hospital, Denmark, over a 5-year period (2016-2020) were identified through the procedure codes for total thyroidectomy. Medical records, pathology reports, biochemical and medical histories were fully assessed for each patient. The primary endpoint was the rate of hypoparathyroidism- both immediate and permanent. Secondary outcomes were parathyroid gland identification rates, rates of parathyroid gland autotransplantation, and rates of inadvertent parathyroid gland excision.ResultsA total of 89 patients were included in the final analysis. A total of 33 patients (37.1%) experienced immediate hypoparathyroidism following surgery, while 30 patients (33.7%) still were on active vitamin D two months postoperatively. One year following surgery, 28 patients (31.5%) were still on active vitamin D and were considered as having permanent hypoparathyroidism. Sixty-one percent of the parathyroid glands were identified intraoperatively, and 19% of the patients experienced parathyroid autotransplantation. Inadvertent parathyroid gland excision occurred for 21% of the patients and was associated with a significantly increased risk of permanent hypoparathyroidism (RR = 2.99; 95% CI: 1.36 – 6.62, p = 0.005).ConclusionBoth transient and permanent hypoparathyroidism following total thyroidectomy at a low-volume, non-parathyroid institution occurred with much higher frequencies than previously reported. The elevated rates were most likely due to the low-volume, non-parathyroid nature of the surgeons which in part was mirrored in low parathyroid gland identifications rates, and high rates of autotransplantation and inadvertent parathyroid gland excision

Differential contributions of specimen types, culturing, and 16S rRNA sequencing in diagnosis of prosthetic joint infections

ABSTRACT Prosthetic joint failure is mainly caused by infection, aseptic failure (AF), and mechanical problems. Infection detection has been improved with modified culture methods and molecular diagnostics. However, comparisons between modified and conventional microbiology methods are difficult due to variations in specimen sampling. In this prospective, multidisciplinary study of hip or knee prosthetic failures, we assessed the contributions of different specimen types, extended culture incubations, and 16S rRNA sequencing for diagnosing prosthetic joint infections (PJI). Project specimens included joint fluid (JF), bone biopsy specimens (BB), soft-tissue biopsy specimens (STB), and swabs (SW) from the prosthesis, collected in situ , and sonication fluid collected from prosthetic components (PC). Specimens were cultured for 6 (conventional) or 14 days, and 16S rRNA sequencing was performed at study completion. Of the 156 patients enrolled, 111 underwent 114 surgical revisions (cases) due to indications of either PJI ( n = 43) or AF ( n = 71). Conventional tissue biopsy cultures confirmed PJI in 28/43 (65%) cases and refuted AF in 3/71 (4%) cases; one case was not evaluable. Based on these results, minor diagnostic adjustments were made. Fourteen-day cultures of JF, STB, and PC specimens confirmed PJI in 39/42 (93%) cases, and 16S rRNA sequencing confirmed PJI in 33/42 (83%) cases. One PJI case was confirmed with 16S rRNA sequencing alone and five with cultures of project specimens alone. These findings indicated that JF, STB, and PC specimen cultures qualified as an optimal diagnostic set. The contribution of sequencing to diagnosis of PJI may depend on patient selection; this hypothesis requires further investigation. </jats:p

No beneficial effects of vitamin D supplementation on muscle function or quality of life in primary hyperparathyroidism:results from a randomized controlled trial

ContextImpairments of muscle function and strength in patients with primary hyperparathyroidism (PHPT) are rarely addressed, although decreased muscle function may contribute to increased fracture risk.ObjectiveWe aimed to assess the changes in muscle strength, muscle function, postural stability, quality of life (QoL), and well-being during treatment with vitamin D or placebo before and after parathyroidectomy (PTX) in PHPT patients.DesignA randomized placebo-controlled trial.PatientsWe included 46 PHPT patients, mean age 58 (range 29–77) years and 35 (76%) were women.InterventionsDaily treatment with 70 μg (2800 IU) cholecalciferol or placebo for 52 weeks. Treatment was administered 26 weeks before PTX and continued for 26 weeks after PTX.Main outcome measuresChanges in QoL and measures of muscle strength and function.ResultsPreoperatively, 25-hydroxyvitamin D (25OHD) increased significantly (50–94 nmol/l) compared with placebo (57–52 nmol/l). We did not measure any beneficial effects of supplementation with vitamin D compared with placebo regarding well-being, QoL, postural stability, muscle strength, or function. In all patients, we measured marked improvements in QoL, well-being (P&lt;0.01), muscle strength in the knee flexion and extension (P&lt;0.001), and muscle function tests (P&lt;0.01) after surgical cure. Postural stability improved during standing with eyes closed (P&lt;0.05), but decreased with eyes open (P&lt;0.05).ConclusionsPatients with PHPT and 25OHD levels around 50 nmol/l did not benefit from vitamin D supplementation concerning muscle strength, muscle function, postural stability, well-being, or QoL. Independent of preoperative 25OHD levels, PTX improved these parameters.</jats:sec