Aliya Khan

Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop

OBJECTIVE Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to guide the use of diagnostics and management for this condition in clinical practice. PARTICIPANTS Interested professional societies selected representatives for the consensus committee and provided funding for a one-day meeting. A subgroup of this committee set the program and developed key questions for review. Consensus was established at a closed meeting that followed and at subsequent discussions. EVIDENCE Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting. CONSENSUS PROCESS Consensus was achieved by a group meeting. Statements were prepared and reviewed by all authors who represented the Planning Committee and the participating professional societies.

Bisphosphonate Associated Osteonecrosis of the Jaw

In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%–12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research.

Recent advances in understanding the epidemiology, genetics, diagnosis, clinical presentations, skeletal involvement, and therapeutic approaches to hypoparathyroidism led to the First International Workshop on Hypoparathyroidism that was held in 2009. At this conference, a group of experts convened to discuss these issues with a view towards a future research agenda for this disease. This review, which focuses primarily on hypoparathyroidism in the adult, provides a comprehensive summary of the latest information on this disease.

Medical Management of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Third International Workshop

BACKGROUND Primary hyperparathyroidism (PHPT) is a common endocrine disorder that is frequently asymptomatic. The 2002 International Workshop on Asymptomatic PHPT addressed medical management of asymptomatic PHPT and summarized the data on nonsurgical approaches to this disease. At the Third International Workshop on Asymptomatic PHPT held in May 2008, this subject was reviewed again in light of data that have since become available. We present the results of a literature review of advances in the medical management of PHPT. METHODS A series of questions was developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies evaluating the management of PHPT with bisphosphonates, hormone replacement therapy, raloxifene, and calcimimetics was conducted. Existing guidelines and recent unpublished data were also reviewed. All selected relevant articles were reviewed, and the questions developed by the International Task Force were addressed by the Consensus Panel. RESULTS Bisphosphonates and hormone replacement therapy are effective in decreasing bone turnover in patients with PHPT and improving bone mineral density (BMD). Fracture data are not available with either treatment. Raloxifene also lowers bone turnover in patients with PHPT. None of these agents, however, significantly lowers serum calcium or PTH levels. The calcimimetic cinacalcet reduces both serum calcium and PTH levels and raises serum phosphorus. Cinacalcet does not, however, reduce bone turnover or improve BMD. CONCLUSIONS Bisphosphonates and hormone replacement therapy provide skeletal protection in patients with PHPT. Limited data are available regarding skeletal protection in patients with PHPT treated with raloxifene. Calcimimetics favorably alter serum calcium and PTH in PHPT but do not significantly affect either bone turnover or BMD. Medical management of asymptomatic PHPT is a promising option for those who are not candidates for parathyroidectomy.

Standards and Guidelines for Performing Central Dual-Energy X-Ray Absorptiometry in Premenopausal Women, Men, and Children: A Report From the Canadian Panel of the International Society of Clinical Densitometry

The Canadian Panel of the International Society for Clinical Densitometry has developed standards in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. Previously, this group addressed the performance of densitometry in postmenopausal women. This report addresses the use of densitometry in men, premenopausal women, and children with a focus on dual-energy X-ray absorptiometry.

The Diagnosis and Management of Asymptomatic Primary Hyperparathyroidism Revisited

Department of Medicine (A.A.K.), McMaster University, Hamilton, Canada L8S 4L8; Departments of Medicineand Pharmacology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032;and Department of Medicine (J.T.P.), Harvard Medical School, Massachusetts General Hospital, Boston Massachusetts02114

Medical Management of Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism

OBJECTIVE Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The only available definitive therapy is parathyroidectomy, which is appropriate to consider in all patients. The purpose of this report is to provide an update on calcium and vitamin D supplementation and medical management for those patients with PHPT who cannot or do not want to undergo surgery. METHODS Questions were developed by the International Task Force on PHPT. A comprehensive literature search was undertaken, and relevant articles published between 2008 and 2013 were reviewed in detail. The questions were addressed by the panel of experts, and consensus was established at the time of the workshop. CONCLUSIONS The recommended calcium intake in patients with PHPT should follow guidelines established for all individuals. It is not recommended to limit calcium intake in patients with PHPT who do not undergo surgery. Patients with low serum 25-hydroxyvitamin D should be repleted with doses of vitamin D aiming to bring serum 25-hydroxyvitamin D levels to ≥ 50 nmol/L (20 ng/mL) at a minimum, but a goal of ≥75 nmol/L (30 ng/mL) also is reasonable. Pharmacological approaches are available and should be reserved for those patients in whom it is desirable to lower the serum calcium, increase BMD, or both. For the control of hypercalcemia, cinacalcet is the treatment of choice. Cinacalcet reduces serum calcium concentrations to normal in many cases, but has only a modest effect on serum PTH levels. However, bone mineral density (BMD) does not change. To improve BMD, bisphosphonate therapy is recommended. The best evidence is for the use of alendronate, which improves BMD at the lumbar spine without altering the serum calcium concentration. To reduce the serum calcium and improve BMD, combination therapy with both agents is reasonable, but strong evidence for the efficacy of that approach is lacking.

Bone Densitometry: Applications and Limitations

Osteoporosis is clinically diagnosed in its advanced stages, usually following a fracture. Accurate, precise, and noninvasive skeletal assessment is now possible for early detection of osteoporosis at a preclinical stage. Currently, the gold standard in bone mass measurement and fracture prediction is dual energy X-ray absorptiometry (DEXA) of the hip and spine. Exponential increases in fracture risk have been observed with small decreases in bone mineral density. Bone mineral density (BMD) should be considered in conjunction with independent clinical risk factors for fracture, including: low body weight, history of postmenopausal fracture, family history of fracture, and poor neuromuscular function. The World Health Organization (WHO) diagnostic criteria for osteoporosis and osteopenia are appropriate for postmenopausal Caucasian women and are applicable to DEXA assessments at the hip, spine, or forearm. This review explores the relationship between BMD and fracture risk, the principles of bone densitometry interpretation, and the applications as well as the limitations of DEXA technology, and presents cases illustrating common errors seen in the interpretation of DEXA studies.

Bone Densitometry in Premenopausal Women: Synthesis and Review

Bone loss prior to menopause is being increasingly identified in women. Clearly, low bone mineral density (BMD) is a significant risk factor for fracture in the estrogen-deficient female postmenopause. The significance of low bone density prior to menopause needs to be addressed. Low bone density in the premenopausal female may reflect attainment of a lower peak bone mass. It may also be secondary to progressive bone loss following achievement of peak bone density. The etiology of low bone density in the premenopausal female needs to be clarified with meticulous exclusion of secondary causes of bone loss. Menstrual status is an important determinant of peak bone mass as well as the development of bone loss in women prior to the onset of menopause. Subclinical decreases in circulating gonadal steroids may be associated with a lower peak bone mass as well as progressive bone loss in otherwise reproductively normal women. Elevations of follicle-stimulating hormone (FSH) of greater than 20 miu/L are associated with evidence of increased bone turnover marker activity and correlate with progressive bone loss in perimenopausal women. This transitional period requires further study with respect to the magnitude of bone loss experienced and the potential benefits of antiresorptive therapy. Detailed assessment of menstrual status is necessary in the evaluation of low bone density in premenopausal women. The majority of the cross-sectional and longitudinal studies completed evaluating BMD in the premenopausal years suggest that minimal bone loss does occur prior to menopause after attainment of peak bone mass. The magnitude of premenopausal bone loss, however, is controversial and may be site-dependent. More rapid rates of bone loss are seen in the transitional period beginning 2-3 yr prior to the onset of menopause. Prospective data are needed to understand further the relationship between BMD and fracture in the premenopausal period. Women with steroid-induced bone loss as well as other secondary causes of osteoporosis respond to antiresorptive therapy with documented improvements in BMD. Biomarkers can identify perimenopausal women with increased bone turnover. Lifestyle modification can improve BMD in the pre- and the perimenopausal period. Antiresorptive therapy has not been evaluated in pre- or perimenopausal women with low BMD in the absence of secondary causes of osteoporosis. As new treatment options are evaluated and become available, biomarker assessment may be of value in identifying women at risk of fracture.

Diagnosis and management of primary hyperparathyroidism

#### Summary points Primary hyperparathyroidism is the most common cause of hypercalcaemia in the ambulatory setting.1 2 Although this condition can occur at any age, it commonly affects people over the age of 50 years and postmenopausal women.2 3 Over the past few decades it has changed from being a condition usually defined by its symptoms to one that is often discovered on routine screening tests while the patient is still largely asymptomatic. In light of advances in research, new guidelines on the diagnosis and management of asymptomatic primary hyperparathyroidism have recently been developed. We review the presentation, diagnosis, and management of primary hyperparathyroidism for the generalist doctor, with evidence drawn from randomised controlled trials, cohort studies, and the most recent consensus guidelines. #### Sources and selection criteria We searched Medline from 2002 to 2011 using the terms “primary hyperparathyroidism”, “diagnosis”, and “management of primary hyperparathyroidism”. We reviewed all relevant articles as well as the proceedings from …