Use of bone turnover markers in the management of osteoporosis.

PURPOSE OF REVIEW: Osteoporosis is a common public health problem that is often undertreated and underdiagnosed. The clinical management of osteoporosis is often reactionary to devastating fracture events. Bone turnover markers may improve the ease and rapidity at which osteoporosis is monitored and treated. Bone turnover markers are biochemical byproducts of bone formation or bone resorption. The clinical use of bone turnover markers is limited by significant preanalytical variability. Effective interpretation of bone turnover markers requires a detailed understanding of the variables that can affect their responses to osteoporosis treatment and monitoring. RECENT FINDINGS: Progress is continuously being made on the standardization of bone turnover markers. The literature on the response of bone turnover markers to unique clinical situations is expanding. Data for evidence-based reference intervals for bone turnover markers has increased. Variables that affect the appropriate timing of lab draws like diurnal variation, postprandial status, exercise and alcohol use have been described. Studies examining the expected response of bone turnover markers to treatments of osteoporosis and other medications that affect bone health continue to increase. SUMMARY: Bone turnover markers have clinical utility in the comprehensive evaluation of osteoporosis. When interpreted with caution and with a good understanding of their natural variability, bone turnover markers provide information that supplements osteoporosis management and provides useful clinical information about conditions that alter bone turnover.

THE USE OF VITAMINS AND MINERALS IN SKELETAL HEALTH: AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND THE AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT.

ABBREVIATIONS: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; CV = cardiovascular; GI = gastrointestinal; IOM = Institute of Medicine; PTH = parathyroid hormone; RCT = randomized controlled trial; αTF = α-tocopherol; ucOC = undercarboxylated osteocalcin; VKA = vitamin K antagonist; WHI = Women's Health Initiative.

Proceedings of the 2016 Santa Fe Bone Symposium: New Concepts in the Management of Osteoporosis and Metabolic Bone Diseases.

The Santa Fe Bone Symposium is an annual meeting of healthcare professionals and clinical researchers that details the clinical relevance of advances in knowledge of skeletal diseases. The 17th Santa Fe Bone Symposium was held in Santa Fe, New Mexico, USA, on August 5-6, 2016. The program included plenary lectures, oral presentations by endocrinology fellows, meet-the-professor sessions, and panel discussions, all aimed to provide ample opportunity for interactive discussions among all participants. Symposium topics included recent developments in the translation of basic bone science to patient care, new clinical practice guidelines for postmenopausal osteoporosis, management of patients with disorders of phosphate metabolism, new and emerging treatments for rare bone diseases, strategies to enhance fracture healing, and an update on Bone Health Extension for Community Healthcare Outcomes, using a teleconferencing platform to elevate the level of knowledge of healthcare professionals in underserved communities to deliver best practice care for skeletal diseases. The highlights and important clinical messages of the 2016 Santa Fe Bone Symposium are provided herein by each of the faculty presenters.

Comparison of the efficacy, adverse effects, and cost of zoledronic acid and denosumab in the treatment of osteoporosis.

OBJECTIVE: Injectable osteoporosis drugs are increasing in popularity due to their efficacy and convenient administration. In this retrospective comparison of the two available treatments, denosumab (Prolia®) and zoledronic acid (ZA, Reclast®), we aimed to determine and compare the efficacy and tolerability of denosumab and ZA. METHODS: The charts of patients who received denosumab and ZA at Loyola Hospital were reviewed, and adverse events were noted. Of primary interest were myalgias, flu-like symptoms, back pain, and fractures. A questionnaire regarding the efficacy, tolerability, and treatment cost supplemented this chart review in a subset of study participants. Bone mineral density (BMD) changes, bone turnover markers, and questionnaire results were also compared. RESULTS: The study cohort consisted of 107 patients (51 denosumab, 56 ZA). The denosumab group had a greater mean increase in spine BMD at 1 year (0.060 g/cm2) than the ZA group (0.021 g/cm2; P = .04). The change in femur and spine BMD at 1 year were not significantly different between the 2 groups. The ZA group had a significantly greater incidence of mild flu-like symptoms (29% ZA group vs. 0% denosumab group; P = .04). CONCLUSION: The denosumab group had a higher mean increase in spine BMD, and the ZA group had a higher incidence of flu-like symptoms, but the study groups were statistically similar in terms of patient satisfaction. As denosumab is still a relatively new therapy, there were a limited number of patients with posttreatment data available for comparison. As more posttherapy data become available, it can be further investigated.

Calcium use in the management of osteoporosis: continuing questions and controversies.

Calcium is a vital element in the health and maintenance of growing and mature bone. The amount of calcium recommended for ingestion varies by age, and these requirements can be met by dietary sources or calcium supplementation. This article reviews the role of calcium in the body and the benefits and risks to calcium supplementation. The effects of calcium on fracture risk reduction, bone density, and bone turnover markers as well as the conflicting data on cardiovascular events and increased risk of nephrolithiasis associated with supplementation are discussed.

Disorders of bone and bone mineral metabolism.

Metabolic bone disorders are very common in the general population and untreated, they can cause a variety of neurologic symptoms. These diseases include osteoporosis, vitamin D deficiency, Paget's disease, and alterations in calcium, phosphorus, and magnesium metabolism. Diagnosis is made through analysis of metabolic bone blood chemistries as well as radiologic studies such as dual energy X-ray absorptiometry (DXA) scans, bone scans, and X-rays. Treatment options have advanced significantly in the past decade for osteoporosis and Paget's disease and mainly include antiresorptive therapy. New recommendations for treatment of primary hyperparathyroidism are discussed as well as therapy for calcium, phosphorus, and mineral disorders.

A Closer look at calcium absorption and the benefits and risks of dietary versus supplemental calcium.

OBJECTIVE: To perform a thorough search of the literature on calcium research and specifically address the topic of calcium absorption. METHODS: PubMed and Ovid were the main engines used for primary literature searches; textbooks, review articles, and book chapters are examples of the other sources used for supplemental information. RESULTS: Regarding calcium absorption, it seems apparent that the absorption efficiency of all calcium salts, regardless of solubility, is fairly equivalent and not significantly less than the absorption efficiency of dietary calcium. However, dietary calcium has been shown to have greater impact in bone building than supplemental calcium. This is likely due to improved absorption with meals and the tendency of people to intake smaller amounts more frequently, which is more ideal for the body's method of absorption. In addition, the cardiovascular risks of excessive calcium intake appear to be more closely related to calcium supplements than dietary calcium; this relationship continues to be controversial in the literature. CONCLUSIONS: We conclude that further studies are needed for direct comparison of supplemental and dietary calcium to fully establish if one is superior to the other with regard to improving bone density. We also propose further studies on the cardiovascular risk of long-term increased calcium intake and on physician estimates of patients' daily calcium intake to better pinpoint those patients who require calcium supplementation.

Effect of vitamin D therapy on bone turnover markers in postmenopausal women with osteoporosis and osteopenia.

OBJECTIVE: To (1) assess the rate of reduction in bone turnover with vitamin D and bisphosphonate therapies and (2) evaluate the clinical utility of bone-specific alkaline phosphatase (BSAP) in monitoring treatment response. METHODS: We retrospectively reviewed medical records of patients with newly diagnosed osteopenia and osteoporosis from 2002 to 2009 at Loyola University Medical Center. A cohort of postmenopausal women with hip or spine T-scores of less than -1, normal serum creatinine, and no prior vitamin D or bisphosphonate therapy was divided into vitamin D-deficient (n = 29) and vitamin D-sufficient (n = 13) groups. Vitamin D-deficient patients received high-dose vitamin D, whereas vitamin D-sufficient patients received orally administered bisphosphonates. BSAP levels at baseline and 1 year were compared. RESULTS: Vitamin D therapy in the group with vitamin D deficiency led to a 26.7% decrease in BSAP (P<.01). Bisphosphonate therapy in the vitamin D-sufficient group led to a 32.7% decrease in BSAP (P = .01). The magnitude of BSAP change in the 2 study groups (6.74 ± 6.48 µg/L and 8.72 ± 9.94 µg/L) did not differ significantly (P = .45). CONCLUSION: The results of this study suggest that correction of vitamin D deficiency in patients with osteopenia and osteoporosis can lead to a decrease in bone turnover as measured by BSAP and that the magnitude of this reduction is similar to that achieved with orally administered bisphosphonates.

Treatment of adult hypophosphatasia with teriparatide.

OBJECTIVE: To describe the effects of 24 months of teriparatide therapy in an adult with hypophosphatasia, which thus far has no established medical treatment. METHODS: A 75-year-old woman with hypophosphatasia was treated with ergocalciferol and calcium supplements for 2 years. She had sustained multiple spontaneous and low-trauma fractures since she was 10 years old. Baseline biochemical values (and reference ranges) were as follows: serum total alkaline phosphatase ranged from 14 to 17 U/L (30 to 110), bone-specific alkaline phosphatase (BSALP) was 5 U/L (14 to 43), serum phosphorus was elevated at 5.4 mg/dL (2.6 to 4.4), and pyridoxal 5'-phosphate was high at 250 ng/mL (5 to 30). At baseline, she had mild secondary hyperparathyroidism (intact parathyroid hormone, 76 pg/mL; reference range, 10 to 65), which was corrected by the calcium supplementation and vitamin D therapy. Dual-energy x-ray absorptiometry (DXA) scanning in 2003 showed L1-L4 bone mineral density (BMD) of 0.786 g/cm2, T score of -3.3, and Z score of -1.7; DXA also showed femoral neck BMD of 0.740 g/cm2, T score of -2.5, and Z score of -0.5. During walking, the patient sustained a low-trauma fracture in a metatarsal. Teriparatide, synthetic parathyroid hormone(1-34), in a dosage of 20 microg subcutaneously was given daily from April 2004 until June 2006. RESULTS: After about 1.5 years of teriparatide therapy, BSALP reached the lower end of the reference range at 16 U/L, and after 24 months of continuous teriparatide treatment, both serum total alkaline phosphatase and BSALP normalized at 30 U/L and 18 U/L, respectively. Pyridoxal 5'-phosphate declined from a baseline of 250 to 188 ng/mL after 17 months of treatment. Urinary N-telopeptide increased from a baseline of <6 to 19 after 17 months and to 70 bone collagen equivalents/mmol creatinine after 24 months of anabolic therapy. Repeated DXA scanning showed a substantial improvement in lumbar spine BMD and stability in hip BMD. The patient experienced no clinical fractures or adverse events during teriparatide therapy. CONCLUSION: In one woman with adult hypophosphatasia, 2 years of teriparatide treatment improved biochemical markers of bone remodeling and increased skeletal mineralization. Teriparatide may prove to be a viable treatment for adult hypophosphatasia; thus, this intervention warrants further evaluation.