Osteoporosis: Schwartz EN

Hans DB, Shepherd JA, Schwartz EN, Reid DM, Blake GM, Fordham JN, Fuerst T, Hadji P, Itabashi A, Krieg MA, Lewiecki EM. · Geneva University Hospital, Geneva, Switzerland. <> · J Clin Densitom. · Pubmed #18442759 No free full text.

Abstract: Peripheral assessment of bone density using photon absorptiometry techniques has been available for over 40 yr. The initial use of radio-isotopes as the photon source has been replaced by the use of X-ray technology. A wide variety of models of single- or dual-energy X-ray measurement tools have been made available for purchase, although not all are still commercially available. The Official Positions of the International Society for Clinical Densitometry (ISCD) have been developed following a systematic review of the literature by an ISCD task force and a subsequent Position Development Conference. These cover the technological diversity among peripheral dual-energy X-ray absorptiometry (pDXA) devices; define whether pDXA can be used for fracture risk assessment and/or to diagnose osteoporosis; examine whether pDXA can be used to initiate treatment and/or monitor treatment; provide recommendations for pDXA reporting; and review quality assurance and quality control necessary for effective use of pDXA.

Schwartz EN, Steinberg DM. · The Northern California Institute for Bone Health, Inc., 3100 Telegraph Avenue, Suite 3000, Oakland, CA 94609, USA. · Curr Osteoporos Rep. · Pubmed #17112425 No free full text.

Abstract: Clinical decision rules (CDRs) are designed to help physicians practice better. A number of CDRs to assist in identifying women with low bone mass have been developed since the mid 1990s, including SCORE, OST (OSTA), OSIRIS, SOFSURF, NOF, ABONE, pBW, ORAI, and weight-only-EPIDOS (which we have termed WO-E). This review discusses these CDRs in terms of development and validation cohorts and their sensitivity and specificity. The sensitivities of the available CDRs exceed 80% and specificities are about 50%. After much analysis, it appears that most experts prefer OST for its simplicity and SCORE for its flexibility, but there is no consensus on what risk factors to use in the CDRs and what regions of interest (spine, total hip, femoral neck, or a combination) to test with dual-energy x-ray absorptiometry (DXA). Because of the lack of consensus, there are barriers to the clinical application of these CDRs. Agreement on a single CDR for worldwide use is required to optimally fulfill the objective of identifying low bone mass.

Schwartz EN, Steinberg D. · The Northern California Institute for Bone Health, Inc., 3100 Telegraph Avenue, Suite 3000, Oakland, CA 94609, USA. · Curr Osteoporos Rep. · Pubmed #16303112 No free full text.

Abstract: Despite the importance of vertebral compression fractures, there is much that remains uncertain. There is no "gold standard" for the definition which has led to epidemiologic and study differences. Height loss is a way to suspect vertebral fractures but it has its own issues. There are multiple radiographic systems for defining vertebral fractures, both prevalent and incident; risk factors for prevalent fractures have already been delineated. Recent studies have elucidated the risk factors for incident vertebral fractures including age, low weight, late menarche, lower bone mineral density, history of vertebral and nonvertebral fractures, smoking, and use of a walking aid. Fan beam densitometers have had improving ability to image the spine, a procedure now known as vertebral fracture assessment (VFA). Recently (in the United States) a CPT code and reimbursement was established. Yet, many vertebral fractures go undiagnosed, diagnosed but unreported, or reported but not utilized in patient care. Because of this, the International Osteoporosis Foundation developed a Vertebral Fracture Initiative for radiologists and the International Society for Clinical Densitometry began a VFA course. Both teaching programs use the semi-quantitative assessment of Genant to aid the radiologists and clinicians in detecting vertebral fractures.

Sarno M, Sarno L, Baylink D, Drinkwater B, Farley S, Kleerekoper M, Lang R, Lappe J, Licata A, McClung M, Miller P, Nattrass S, Recker R, Schwartz EN, Tucci JR, Wolf S, Powell H, Tjersland G, Warnick GR. · Vision Biotechnology Consulting, Escondido, CA, USA. · Clin Chem Lab Med. · Pubmed #11350019 No free full text.

Abstract: Convenient techniques for measuring rates of bone turnover have been developed in recent years with the advent of biochemical markers of bone metabolism. One recent of these techniques is a collection method and quantitative enzyme immunoassay for free pyridinoline crosslinks in human sweat. The concentrations of pyridinoline crosslinks in 5-day sweat collections and first morning void and 24-hour urine collections from healthy subjects and subjects with established metabolic bone disorders were determined. T-scores were higher in the sweat system than in the urine system by up to 10-fold in postmenopausal subjects, women with hyperparathyroidism, and subjects with postmenopausal osteoporosis. For subjects with postmenopausal osteoporosis, receiver-operating characteristic curve analysis yielded areas under the curve of 0.699, 0.629, and 0.520 for sweat pyridinoline, first morning void urine pyridinoline, and 24 hour urine pyridinoline respectively. The areas under the curve of the sweat and first morning void urine measurements were significantly greater (p<0.05) than the 24-hour pyridinoline measurements. Healthy postmenopausal subjects and subjects with postmenopausal osteoporosis were monitored before and during estrogen replacement therapy or alendronate therapy. Sweat pyridinoline values declined by 49.0 +/- 12.4% and 19.4 +/- 19.9% for estrogen and alendronate subjects respectively. We conclude that this non-invasive technique is a sensitive and specific measure of bone resorption and is appropriate as an adjunct to techniques such as bone density and may also be useful in monitoring of response to anti-resorptive therapies.

Miller PD, Schwartz EN, Chen P, Misurski DA, Krege JH. · Department of Medicine, University of Colorado Health Sciences Center and Colorado Center for Bone Research, Denver, CO, USA. · Osteoporos Int. · Pubmed #17013567 No free full text.

Abstract: INTRODUCTION: The prevalence of both osteoporosis and renal impairment increases with age. METHODS: Using data from the Fracture Prevention Trial, the safety and efficacy of teriparatide [rhPTH(1-34)] in postmenopausal women with osteoporosis and renal impairment were explored. Patients were required to have serum creatinine concentrations < or =2.0 mg/dl and normal serum parathyroid hormone (PTH) concentrations and were randomized to receive daily subcutaneous injections of placebo or teriparatide 20 or 40 mcg/day. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. Patients were defined from baseline assessments to have normal (GFR > or =80 ml/min), mildly impaired (GFR 50-79 ml/min), or moderately impaired (GFR 30-49 ml/min) renal function for bone mineral density (BMD) and amino-terminal extension peptide of procollagen type 1 (PINP) analyses, and normal (GFR > or =80 ml/min) or impaired (GFR <80 ml/min) renal function for fracture analyses. RESULTS AND CONCLUSIONS: Compared with patients with normal renal function, patients with renal impairment were older, shorter, weighed less, had been postmenopausal longer, and had lower baseline lumbar spine and femoral neck BMD. Compared with placebo, teriparatide significantly increased PINP and lumbar spine and femoral neck BMD within each renal function subgroup, and there was no evidence that these increases were altered by renal insufficiency (each treatment-by-subgroup interaction p>0.05). Similarly, teriparatide-mediated vertebral and nonvertebral fracture risk reductions were similar and did not differ significantly between patients with normal or impaired renal function (treatment-by-subgroup interactions p>0.05). The incidences of treatment-emergent and renal-related adverse events were consistent across treatment assignment in the normal, mildly impaired, and moderately impaired renal function subgroups. Teriparatide induced changes in mean GFR were unaffected by baseline renal function (treatment-by-renal function interaction p>0.05 for normal, mildly impaired, or moderately impaired subgroups). Patients in all renal function categories treated with teriparatide 20 or 40 mcg had an increased incidence of 4-6-h postdose serum calcium >10.6 mg/dl (the upper limit of normal) versus placebo; however, teriparatide 20 mcg/day was not associated with significantly increased incidence of 4-6-h postdose serum calcium >11 mg/dl in any renal function category. Teriparatide therapy was associated with increased incidence of elevated uric acid, with the incidences being highest in patients with moderately impaired renal function and in those receiving teriparatide 40 mcg/day. Even so, adverse event data did not suggest an increased incidence of gout or arthralgia or of nephrolithiasis events in teriparatide-treated patients with normal, mild, or moderate renal impairment.

Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, Glass EV, Myers SL, Krege JH. · Cleveland Clinic Foundation, Cleveland, Ohio, USA. · J Bone Miner Res. · Pubmed #16234962 No free full text.

Abstract: We compared combination treatment with teriparatide plus raloxifene with teriparatide alone in women with postmenopausal osteoporosis in a 6-month double-blind, placebo-controlled trial that measured biochemical markers of bone turnover and BMD. Markers of bone formation and spine BMD increased similarly with teriparatide alone and combination therapy. However, combination therapy induced a significantly smaller increase in bone resorption versus teriparatide alone and significantly increased total hip BMD versus baseline. INTRODUCTION: The effects of combining two approved treatments for osteoporosis with different modes of action were examined by comparing teriparatide [rhPTH(1-34)] monotherapy with combination teriparatide and raloxifene therapy. MATERIALS AND METHODS: A 6-month randomized, double-blind trial comparing teriparatide plus raloxifene (n = 69) versus teriparatide plus placebo (n = 68) was conducted in postmenopausal women with osteoporosis. RESULTS: Bone formation (N-terminal propeptide of type 1 collagen [PINP]) increased similarly in both treatment groups. However, the increase in bone resorption (serum C-terminal telopeptide of type I collagen [CTx]) in the combination group was significantly smaller than in the teriparatide-alone group (p = 0.015). Lumbar spine BMD significantly increased 5.19 +/- 0.67% from baseline in the teriparatide-alone group. In the combination group, lumbar spine (6.19 +/- 0.65%), femoral neck (2.23 +/- 0.64%), and total hip (2.31 +/- 0.56%) BMD significantly increased from baseline to study endpoint, and the increase in total hip BMD was significantly greater than in the teriparatide-alone group (p = 0.04). In the teriparatide-alone group, mean serum calcium levels increased from baseline to endpoint (0.30 +/- 0.06 mg/dl, p < 0.001), whereas mean serum phosphate remained unchanged. In the combination group, mean serum calcium was unchanged, and mean serum phosphate decreased (-0.20 +/- 0.06 mg/dl, p < 0.001) from baseline to endpoint. Changes in serum calcium (p < 0.001) and phosphate (p < 0.004) were significantly different between treatment groups. The safety profile of combination therapy was similar to teriparatide alone. CONCLUSIONS: Combination therapy increased bone formation to a similar degree as teriparatide alone. However, the increase in bone resorption was significantly less and total hip BMD significantly increased for combination therapy compared with teriparatide alone. Combination treatment with raloxifene may thus enhance the bone forming effects of teriparatide. Further studies over longer treatment duration that include fracture endpoints are necessary to fully ascertain the clinical significance of combination raloxifene plus teriparatide therapy in postmenopausal osteoporosis.

Abbott TA, Mucha L, Manfredonia D, Schwartz EN, Berger ML. · Outcomes Research & Management, Merk & Co., West Point, PA 19486, USA. · J Clin Densitom. · Pubmed #10548818 No free full text.

Abstract: The purpose of this analysis was to identify efficient (highest sensitivity at each level of cost) strategies to detect osteoporosis in postmenopausal women. Our study sample consisted of 392 women (age >/=50 yr) who were retirees or active employees of a corporation. The Simple Calculated Osteoporosis Risk Estimation (SCORE) questionnaire was completed, and bone mineral density levels were collected at the forearm using peripheral dual X-ray absorptiometry (pDXA), and at the femoral neck and lumbar spine using central DXA. Osteoporotic women were those with a T-score of -2.5 or less at any one of the three skeletal sites tested. Assumed costs were $5 for SCORE, $35 for pDXA, $120 for DXA at either the hip or spine, and $200 for DXA at both the hip and spine. The analysis indicated that the current "gold standard" is inefficient relative to other strategies investigated. By comparison, a tiered strategy consisting of SCORE, pDXA, and then selective use of DXA at both the hip and spine identified 90% of the women with osteoporosis at a cost of only $106 per woman tested. In choosing among the efficient strategies, decision makers must determine the extent to which they are willing to trade off higher program cost for greater sensitivity.