An Endocrine Society Thematic Issue: Bone Research 2023
June 2023
Read our special collection of journal articles, published in 2022–2023, focused on bone research! Curation of the collection was guided by Altmetric Attention Scores and Featured Article designations.
In Journal of the Endocrine Society, Mullin and colleagues describe a functional assessment of calcium-sensing receptor variants from probands provisionally diagnosed with familial hypocalciuric hypercalcemia. It enabled investigators to rule out primary hyperparathyroidism, which can cause osteopenia and osteoporosis. Tests could demonstrate impaired expression of the mature receptor produced by the variant genes. Hamilton and patient coauthors provide a perspective on the needs of patients with X-linked hypophosphatemia, stressing the importance of clinical education and whole-life care. Chuki and associates report frequent disease recurrence in a long-term study of patients treated for primary hyperparathyroidism by autografts of parathyroid tissue into muscle.
In Endocrinology, Daley et al. report the use of a homologous recombination-based knock-in technique to generate a mouse model in which complementary DNA encoding the human parathyroid-1 receptor replaces a segment of the equivalent murine gene, so the human protein is expressed; the model can be used to evaluate the pharmacologic properties of ligands. Hasegawa and colleagues report that the oral calcimimetic evocalcet rescues secondary hyperparathyroidism-driven bone cortical porosity in male rat models of chronic kidney disease. Jiang and associates report data suggesting that intestinal vitamin D receptor in adult mice prevents bone loss during low calcium intake but is dispensable during adequate calcium intake.
In JCEM, Komaba and colleagues report that parathyroidectomy led to better long-term outcomes than cinacalcet treatment in patients with secondary hyperparathyroidism receiving hemodialysis. Seib et al. describe how in a predominantly male cohort with primary hyperparathyroidism, patients treated by parathyroidectomy continued to be at higher risk of kidney stone events in the immediate years after treatment than patients managed nonoperatively, although the adjusted risk of kidney stone events declined with time. Wu et al. report on a study of the long-term effects of medical therapy on over 46,000 patients over 40 who had an osteoporotic fracture. Long-acting zoledronic acid provided the lowest mortality of all the medications studied, with denosumab and alendronate/risedronate also providing improvements over raloxifene and bazedoxifene.
In Endocrine Reviews, Schini and associates assess the benefits from increasing use of bone turnover markers in research and clinical practice. Jha and Simonds review the molecular and clinical spectrum of primary hyperparathyroidism, which in rare cases may be caused by parathyroid carcinoma. And Saul and Khosla summarize the physiological as well as pathological processes during fracture healing in endocrine disease and aging, with the goal of establishing a broad understanding of the biomechanical and molecular mechanisms involved in bone repair.
JOURNAL OF THE ENDOCRINE SOCIETY
Functional Assessment of Calcium-Sensing Receptor Variants Confirms Familial Hypocalciuric Hypercalcemia
In the clinic it is important to differentiate primary hyperparathyroidism (PHPT) from the more benign, inherited disorder, familial hypocalciuric hypercalcemia (FHH). Since the conditions may sometimes overlap biochemically, identification of calcium-sensing receptor (CASR) gene variants causative of FHH (but not PHPT) is the most decisive diagnostic aid. When novel variants are identified, bioinformatics and functional assessment are required to establish pathogenicity.
Whole Body, Whole Life, Whole Family: Patients’ Perspectives on X-Linked Hypophosphatemia
Long-Term Outcomes of Parathyroid Autografts in Primary Hyperparathyroidism
Autologous implantation of parathyroid tissue is frequently utilized after parathyroidectomy in patients with heritable forms of primary hyperparathyroidism (PHPT). Data on long-term functional outcome of these grafts is sparse.
ENDOCRINOLOGY
Actions of Parathyroid Hormone Ligand Analogues in Humanized PTH1R Knockin Mice
Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands and analogues for their pharmacologic activities and potential therapeutic utility toward diseases of bone and mineral ion metabolism.
Evocalcet Rescues Secondary Hyperparathyroidism-driven Cortical Porosity in CKD Male Rats
To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. The treated rats were then divided into vehicle groups and evocalcet administered groups.
Intestinal Vitamin D Receptor Is Dispensable for Maintaining Adult Bone Mass in Mice With Adequate Calcium Intake
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3)-mediated intestinal calcium (Ca) absorption supplies Ca for proper bone mineralization during growth. We tested whether vitamin D receptor (VDR)-mediated 1,25(OH)2D3 signaling is critical for adult Ca absorption and bone by using mice with inducible Vdr gene knockout in the whole intestine (villin-CreERT2+/− × Vdrf/f, WIK) or in the large intestine (Cdx2-CreERT2+/− ×Vdrf/f, LIK). At 4-month-old, Vdr alleles were recombined (0.05 mg tamoxifen/g BW, intraperitoneally [i.p.], 5 days) and mice were fed diets with either 0.5% (adequate) or 0.2% (low) Ca.
THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Parathyroidectomy vs Cinacalcet Among Patients Undergoing Hemodialysis
Parathyroidectomy (PTx) and cinacalcet are both effective treatments for secondary hyperparathyroidism in hemodialysis patients, but limited data exist comparing the long-term outcomes of these interventions.
Kidney Stone Events Following Parathyroidectomy vs Nonoperative Management for Primary Hyperparathyroidism
Primary hyperparathyroidism (PHPT) is associated with an increased risk of kidney stones. Few studies account for PHPT severity or stone risk when comparing stone events after parathyroidectomy vs nonoperative management.
Comparisons Between Different Anti-osteoporosis Medications on Postfracture Mortality: A Population-Based Study
Osteoporosis is becoming a global epidemic in aging societies. Anti-osteoporotic medications can prevent fractures, and their pleiotropic effect on mortality is interesting but not well compared among each other.
ENDOCRINE REVIEWS
Bone Turnover Markers: Basic Biology to Clinical Applications
Bone turnover markers (BTMs) are used widely, in both research and clinical practice. In the last 20 years, much experience has been gained in measurement and interpretation of these markers, which include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide); and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b).
Molecular and Clinical Spectrum of Primary Hyperparathyroidism
Recent data suggest an increase in the overall incidence of parathyroid disorders, with primary hyperparathyroidism (PHPT) being the most prevalent parathyroid disorder. PHPT is associated with morbidities (fractures, kidney stones, chronic kidney disease) and increased risk of death. The symptoms of PHPT can be nonspecific, potentially delaying the diagnosis.
Fracture Healing in the Setting of Endocrine Diseases, Aging, and Cellular Senescence
More than 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration of bone structure is associated with impaired bone healing. Fracture healing is a dynamic process which can be divided into four stages.
