An electronic health record (eHR) review of Veterans with a spinal cord injury and disorder (SCI/D) was conducted to understand the extent to which Veterans Affairs (VA) providers pursue workups for secondary causes of osteoporosis in this population. Laboratory tests for secondary causes were ordered in only one-third of Veterans, with secondary causes identified in two-thirds of those tested, most frequently, hypogonadism and hypovitaminosis D. To identify workups for secondary causes of osteoporosis in SCI/D and the extent to which subspecialty consultations are sought. A total of 3018 prescriptions for an osteoporosis medication (bisphosphonate, calcitonin, denosumab, raloxifene, teriparatide) among 2675 Veterans were identified in fiscal years 2005–2015 from VA administrative databases. Approximately 10% of these prescriptions were selected for eHR review. eHR records of 187 Veterans with a SCI/D who had received pharmacological treatment for osteoporosis were reviewed. Workups for secondary causes of osteoporosis were performed in 31.5% of Veterans (n = 59) with approximately 64.4% of those tested (n = 38) having at least one abnormality. Hypogonadism (52.0% of those tested) and hypovitaminosis D (50.0% of those tested) were the most common secondary causes of osteoporosis identified in this population. Approximately 10% of primary care and SCI providers consulted subspecialists for further evaluation and treatment of osteoporosis. Endocrinologists more frequently performed a workup for secondary causes of osteoporosis compared to other provider specialties. Screening for secondary causes of osteoporosis, particularly for hypogonadism and hypovitaminosis D, should be considered in patients with a SCI/D.

New users of RAAS inhibitors, including ACE inhibitors and ARBs, have a small increased risk for fracture in the first 3 years of use, with a reduced risk of fracture with longer duration of use. Pharmacological inhibitors of the renin-angiotensin aldosterone system (RAAS) are used to treat hypertension. However, the relationship of these medications to osteoporosis is inconsistent, and no study has included simultaneous measurements of both incident fractures and bone mineral density (BMD). The association of RAAS inhibitor use (n = 131,793) with incident fractures in new users of these medications in women in the Women’s Health Initiative over a minimum median follow-up of 6.5 years was assessed by Cox proportional hazard models. The association of incident fractures by a cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated. Subgroup analysis of fracture risk by RAAS inhibitor use confined to women with hypertension was also performed (n = 33,820). The association of RAAS inhibitor use with changes in BMD of the hip was estimated by linear regression in 8940 women with dual energy X-ray absorptiometry measurements. There was no significant association between RAAS inhibitor use and all fractures in the final adjusted multivariable models including hip BMD (HR 0.86 (0.59, 1.24)). However, among users of RAAS inhibitors, including ACE inhibitors and angiotensin receptor blockers (ARBs), hazard ratios for all incident fracture sites in final multivariable models including hip BMD showed dramatic differences by duration of use, with short duration of use (3 years or less) associated with a marked increased risk for fracture (HR 3.28 (1.66, 6.48)) to (HR 6.23 (3.11, 12.46)) and use for more than 3 years associated with a reduced fracture risk (HR 0.40 (0.24, 0.68) to (HR 0.44 (0.20, 0.97)) . Findings were similar in the subgroup of women with a history of hypertension. There was no significant change in BMD of the hip by RAAS inhibitor use. In postmenopausal women, use of RAAS inhibitors, including ACE inhibitors and ARBs, is associated with an increased risk for fracture among new users of these medications in the first 3 years of use. However, long-term use (> 3 years) is associated with a reduced risk. Consideration for fracture risk may be part of the decision-making process for initiation of these medications for other disease states.

Low T-scores at the hip predict incident fractures in persons with a SCI.

There was no association of plasma DPP-4 activity levels with bone mineral density (BMD), body composition, or incident hip fractures in a cohort of elderly community-dwelling adults.

Clinical risk factors for fracture were explored among Veterans with a spinal cord injury. At the end of 11 years of follow-up, the absolute risk of fracture was approximately 20 %. Among the clinical and SCI-related factors explored, a prior history of fracture was strongly associated with incident fracture.

Soluble CD14 (sCD14) is an inflammatory marker associated with osteoclasts. Using Cox proportional hazards models, we found a positive association between plasma levels of sCD14 and risk of incident fracture among participants in the Cardiovascular Health Study. sCD14 may be useful in identifying those at risk for fracture.

Study design: Retrospective review of a clinical database. Objectives: To examine treatment modalities of incident appendicular fractures in men with chronic SCI and mortality outcomes by treatment modality. Setting: United States Veterans Health Administration Healthcare System. Methods: This was an observational study of 1979 incident fractures that occurred over 6 years among 12 162 male veterans with traumatic SCI of at least 2 years duration from the Veterans Health Administration (VA) Spinal Cord Dysfunction Registry. Treatment modalities were classified as surgical or nonsurgical treatment. Mortality outcomes at 1 year following the incident fracture were determined by treatment modality. Results: A total of 1281 male veterans with 1979 incident fractures met inclusion criteria for the study. These fractures included 345 (17.4%) upper-extremity fractures and 1634 (82.6%) lower-extremity fractures. A minority of patients (9.4%) were treated with surgery. Amputations and disarticulations accounted for 19.7% of all surgeries (1.3% of all fractures), and the majority of these were done more than 6 weeks following the incident fracture. There were no significant differences in mortality among men with fractures treated surgically compared with those treated nonsurgically. Conclusions: Currently, the majority of appendicular fractures in male patients with chronic SCI are managed nonsurgically within the VA health-care system. There is no difference in mortality by type of treatment.

Background. Factors contributing to heart failure (HF) in African Americans (AA) are under investigation. Reduced 25(OH)D confers increased cardiovascular risk, including HE Methods: We monitored serum 25(OH)D, 1,25(OH)(2)D-3, parathyroid hormone (PTH), and creatinine clearance in 102 AA residing in Memphis: 58 hospitalized with decompensated HF of >= 4 weeks in 34 (21 men; 53.3 1.8 years) or of 1 to 2 weeks in 24 (17 men; 49.6 +/- 2.4 years) and associated with a dilated cardiomyopathy and reduced ejection fraction (<35%); 19 outpatients with compensated HF (14 men; 52.6 +/- 2.7 years) with comparable ejection fraction; 16 outpatients (9 men; 55.4 +/- 2.9 years) with heart disease, but without HF; and 9 healthy volunteers Q men; 35.8 +/- 3.5 years). Results: Serum 25(OH)D <= 30 ng/mL was found in 96% and 90% with protracted or short-term decompensated HF, where it was of moderate to marked severity (<20 ng/mL) in 83% and 76%, respectively. In patients with either compensated or no HF, 25(OH)D <30 ng/mL was found in 95% and 100%, respectively, and in 30% of volunteers. Normal serum 1,25(OH)(2)D-3 did not differ between patients. Serum PTH >65 pg/mL was found in all AA with decompensated HF of >= 4 weeks (132.4 +/- 12.0 pg/mL) and 67% with 1 to 2 weeks duration (82.3 +/- 7.9 pg/mL), but only 11% with compensated HF (45.8 +/- 6.1 pg/mL), 12% without HF (29.6 +/- 5.4 pg/mL), and none of the volunteers (31.1 +/- 3.9 pg/mL). Creatinine clearance did not differ between patient groups. Conclusions: Hypovitaminosis D is prevalent amongst AA residing in Memphis, with or without HF. Elevations in serum PTH in keeping with secondary hyperparathyroidism are only found in AA with decompensated HF, where hypovitaminosis D and other factors are contributory.

The heart normally is an efficient physiological pump whose muscular compartment is composed of a syncytium of cardiomyocytes nourished by a coronary vasculature and housed within a scaffolding of structural proteins. The contractile properties of cardiomyocytes are governed by the direct interplay between Ca2+ and contractile proteins, actin and myosin, and their intracellular handling of Ca2+. Likewise, extracellular Ca2+ handling, or Ca2+ homoeostasis, can indirectly influence cardiomyocyte contractility. Herein, we briefly examine Ca2+ dyshomoeostasis and heart failure. Plasma Ca2+ concentrations are highly regulated and maintained within a narrow range. If disturbed, a series of controlling factors and feedback mechanisms are called into play. Overall Ca2+ homoeostasis relates to its dietary intake; absorption and excretion from gut and kidneys; bone storage; and the modifying influence of such calcitropic hormones as calcitriol (activated vitamin D) and parathyroid hormone (PTH). In utero, the availability of Ca2+ for fetal growth and development, including the bony skeleton, depends on maternal factors such as: ( a ) dietary Ca2+ intake, which may be reduced, particularly in vegans or in some women with lactose intolerance, who avoid dairy products; ( b ) urinary and fecal Ca2+ losses; ( c ) Ca2+ bone stores that may be mobilised if Ca2+ availability is compromised; and ( d ) vitamin D status, as assessed by serum 25-hydroxyvitamin D (25-(OH)D) levels. 25-(OH)D levels are chiefly dependent on supplementation and sunlight exposure that may be limited by culturally imposed dress code, skin pigmentation, where melanin is a natural sunscreen that mandates longer exposure to the UVB component of sunlight to generate vitamin D, senescent skin less able to produce vitamin D, obesity where adipocytes sequester it, the altitude, latitude and locale (urban vs rural) of …

Objective: We previously noted secondary hyperparathyroidism (SHPT) in African-American patients hospitalized during February, 2005 with either untreated or treated congestive heart failure (CHF) due to ischemic or idiopathic cardiomyopathy. Herein, we hypothesized that housebound African-American patients hospitalized during the period of June I through August 31, 2005, with CHF would have SHPT and hypovitaminosis D. Methods: Twenty-five African-American patients with an ejection fraction (EF) less than 35% due to ischemic or dilated (idiopathic) cardiomyopathy were monitored: 20 were hospitalized with CHF, stratified on historical grounds as of 4 weeks' or longer duration or of 1 to 2 weeks' duration in 11 and 9 patients, respectively, despite medical care that included furosemide; serum parathyroid hormone (PTH) and 25(OH)D at the time of admission in these patients were compared to five asymptomatic outpatients seen during the summer with stable, compensated failure. Results: Serum PTH was elevated (127 +/- 13; 82-243 pg/mL) in all patients with CHF of 4 weeks' or longer duration (normal, 12-65 pg/mL) and was elevated in three of nine patients (59 +/- 8; 18-99 pg/mL) with CHF of 1 to 2 weeks' duration. Ionized hypocalcemia (1.09 +/- 0.03 and 1.08 +/- 0.02 mmol/L; normal, 1.12-1.30) and hypomagnesemia (0.47 +/- 0.02 and 0.46 +/- 0.03 mmol/L; normal, 0.53-0.67) were respectively found in long- or short-duration CHF. No compensated patient had elevated PTH (42 +/- 5; 17-53). Hypovitaminosis D (<= 30 ng/mL) was universally present in patients with CHF of 4 weeks' or longer duration (15.1 +/- 1.4; 7.0-23.8 ng/mL) and was also prevalent in the other groups (20.3 +/- 5.1, 7.0-54.1 ng/mL in CHF of 1 to 2 weeks' duration and 23.1 +/- 4.9; 17.2-42.7 ng/mL in compensated failure). Conclusions: In African-American patients with CHF, hypovitaminosis D, aldosteronism, and loop diuretic treatment each exaggerate Ca 21 and Mg2+ losses to stress a fragile Ca2+ balance leading to ionized hypocalcemia and hypomagnesemia with SHPT.

Purpose Congestive heart failure (CHF), with aldosteronism, includes a systemic illness. Our working hypothesis of this illness invokes secondary hyperparathyroidism (SHPT) induced by exaggerated urinary and fecal losses of Ca2+ and Mg2+ and their fallen plasma-ionized levels that accompany aldosteronism and furosemide treatment. We previously found serum parathyroid hormone (PTH) levels to be elevated in predominantly African American (AA) patients hospitalized during the winter (February 2005) because of their symptomatic CHF. However, we did not discount hypovitaminosis D. Melanin is a natural sunscreen. Herein we hypothesized that housebound AA, who were hospitalized during June 1-August 31, 2005 with chronic, treated CHF, would have SHPT and hypovitaminosis D. Methods Twenty-five AA (50.6 6 2.3 years; 9 women) with systolic dysfunction (EF < 35%) due to ischemic or dilated cardiomyopathy were monitored: 20 were hospitalized with signs and symptoms of CHF, stratified on historical grounds as protracted CHF ($ 4 wk) in 11 or of short duration (1-2 wk) in 9. Patients with CHF had been treated with an ACE inhibitor or AT1 receptor antagonist, furosemide, and in many cases spironolactone. Serum PTH and 25(OH)D, obtained in these 20 patients within 48 hours of admission, were compared to 5 asymptomatic outpatients with stable, compensated failure seen during this time period and who were similarly treated. Results Serum PTH in the 11 AA with protracted decompensated failure (127 6 13; 82-243 pg/mL) was greater than the normal range (12-65 pg/mL); it was elevated in 3 of 9 with short-term CHF (59 6 8; 18-99 pg/mL). In both groups with CHF, ionized hypocalcemia (1.09 6 0.03 and 1.08 6 0.02 mmol/L; normal 1.12-1.30) and ionized hypomagnesemia (0.47 6 0.02 and 0.46 6 0.03 mmol/L; normal 0.53-0.67) were found. None of the compensated patients had elevated PTH (42 6 5; 17-53 pg/mL). Hypovitaminosis D (# 30 ng/mL) was seen in all 11 with protracted CHF (15.1 6 1.4; 7.0-23.8 ng/mL); 8 of 9 with short-duration CHF (20.3 6 5.1; 7.0-54.1 ng/mL); and 4 of 5 with compensated failure (23.1 6 4.9; 17.2-42.7 ng/mL). Conclusions In housebound AA with symptomatic CHF, hypovitaminosis D is prevalent, even during the summer. The aldosteronism of protracted CHF and chronic furosemide use each exaggerate Ca2+ and Mg2+ losses to compromise cation balance, leading to ionized hypocalcemia and hypomagnesemia with SHPT. Raising 25(OH)D levels in AA with CHF remains to be addressed.

OBJECTIVE:To determine bone mineral content (BMC), bone mineral density (BMD), Z scores, and markers of bone turnover in African American children with juvenile rheumatoid arthritis (JRA).METHODS:Eight children with JRA with no prior exposure to corticosteroids were evaluated. Lumbar spine (L1-L4) and total body and total hip BMC and BMD were determined using dual x-ray absorptiometry (DXA), and Z scores (BMD) were calculated. Serum samples of markers of bone turnover including pyridinoline (PYR), N-terminal propeptide of type I procollagen (P1NP), osteocalcin (OC), and bone-specific alkaline phosphatase (BSAP) were measured.RESULTS:The mean Z score (BMD) at the lumbar spine (L1-L4) in patients with JRA was -1.2+/-0.8. Z scores for total body and total hip were within 1 standard deviation of normal compared with healthy historical controls matched for age, sex, and race.CONCLUSION:BMD was normal for chronological age (defined as Z score >or= 2.0) in African American children with JRA who had not previously been treated with corticosteroids. Further studies are needed on the effects of JRA on skeletal health in African American children.

Purpose Congestive heart failure (CHF) features a disabling systemic illness that includes oxidative stress and a proinflammatory phenotype. Endogenous antioxidant defenses, integral to combating superoxide and H2O2, include cytosolic superoxide dismutase and glutathione peroxidase and which are Zn and Se dependent, respectively. Serum Zn and Se balance in patients with CHF remain uncertain. Urinary Zn excretion is increased in hyperparathyroidism (HPT) as well as in response to treatment with an angiotensin-converting enzyme inhibitor (ACEI), an AT1 receptor antagonist (AT1Ra), and a thiazide but not loop diuretic. We therefore hypothesized a deficiency of Zn and Se in CHF. Methods We monitored serum Zn, Se, and parathyroid hormone (PTH) in 25 AA (50.6 6 2.3 yrs; 16 men) with systolic dysfunction (EF < 35%) due to ischemic or dilated (idiopathic) cardiomyopathy; 20 were hospitalized because of signs and symptoms of CHF, who were further stratified on historical grounds as having decompensated (D) failure of long ($ 4 wks) or short (1-2 wks) duration in 11 and 9, respectively, despite medical care that included ACEI or AT1Ra, a loop diuretic and spironolactone; and 5 were outpatients with treated, compensated failure (Comp). Results (mean 6 SEM): Conclusions In AA, either hospitalized with CHF or followed as outpatients with compensated heart failure, all of whom were treated with an ACEI or AT1Ra, we found hypozincemia and hyposelenemia. It remains to be determined if the observed fall in serum Zn and Se reflects increased renal and/or colonic excretion of these micronutrients related to secondary HPT and/or medications, a dietary deficiency, and/or their redistribution within tissues related to up-regulated expression of binding proteins. A role for dietary supplementation of Zn and Se in AA patients with CHF remains to be addressed.

Purpose Emerging data implicate an important interrelationship between cardiovascular disease and osteoporosis. Data from our institution extend this finding to include a linkage between congestive heart failure (CHF) and osteoporosis and suggest that disturbances in the vitamin D/parathyroid axis, particularly in African Americans (AA), may play a pivotal role in the pathogenesis of both CHF and bone loss. However, little is known about the epidemiology of osteoporotic-related fractures that occur in the setting of CHF. Methods The medical records review of all male patients with a diagnosis of CHF and hip fractures hospitalized at Veterans Administration Medical Center, Memphis, TN, between 1999 and 2005 were reviewed to determine characteristics of these fractures and subsequent treatment for osteoporosis. The protocol was approved by the Institutional Review Board at the VA Medical Center, Memphis, TN. Results 3,424 patients with an ICD-9 diagnosis of CHF between January 1999 and July 2005 were identified; of these 86 had an ICD-9 diagnosis of hip fracture (not pathological). Fifty patients were excluded for the following reasons: female (n = 2); hip fracture was traumatic (n = 2); no record of hip fracture (n = 9) or record of CHF (n = 4) noted in chart; insufficient information available concerning hip fracture (n = 4); cancer (n = 29). This left a study population of 36 individuals, none of whom had any condition known to affect bone metabolism. The mean age of these male veterans with hip fractures was 69 (range 47-87); 25% of these fractures occurred in AA. Nineteen percent of these veterans had at least two atraumatic fractures during the time period of this study; in 6%, this second fracture was a contralateral hip fracture. Hip fracture location was approximately equally divided between femoral neck and intertrochanteric fractures. During the time period of this study, following their hip fracture, only three patients had a DXA or QCT scan measured, and in only one patient was therapy with a bisphosphonate or teriparatide initiated. Conclusions Hip fractures in male veterans with CHF occur in both AA and Caucasians and are seriously underrecognized as a marker for osteoporosis and future fractures. Treatment to prevent future fractures in these patients needs to be adequately addressed.

BackgroundThe congestive heart failure syndrome includes a systemic illness with wasting of soft tissues and bone. We hypothesized secondary hyperparathyroidism (HPT) would be found in hospitalized patients with decompensated congestive heart failure (CHF), where secondary aldosteronism is expected, and who were either untreated or treated medically.MethodsIn 9 consecutive patients (7 males, 2 females; 8 African-American, 1 Caucasian; 33–60 yrs) admitted to the Regional Medical Center during a 28-day period with chronic left ventricular systolic dysfunction (EF<35%) and decompensated CHF (5 untreated; 4 treated with an angiotensin converting enzyme inhibitor, furosemide, and small-dose spironolactone), we measured: plasma parathyroid hormone (PTH); serum calcium corrected for albumin, magnesium, and phosphorus; serum creatinine and calculated creatinine clearance.ResultsPlasma PTH was elevated above the normal range (6-65 pg/mL) in both untreated and treated patients with CHF (204±60 and 134±14 pg/mL, respectively). Serum corrected calcium was normal (8.4-10.2 mg/dL) in both untreated and treated CHF (9.7±0.l and 9.1±0.2 mg/dL, respectively) as were serum magnesium and phosphorus. Calculated creatinine clearance did not differ between untreated and treated patients (74±15 and 83±21 mL/min, respectively).ConclusionsSecondary HPT was found in 5 untreated and 4 treated patients consecutively hospitalized over a 28-day period with decompensated CHF. Corrected serum calcium was normal. Plasmaionized calcium, a determinant of PTH secretion, was not measured. Although vitamin D levels were not assessed, the presence of hypovitaminosis D in these housebound patients with symptomatic CHF cannot be discounted. HPT may contribute to the systemic illness that accompanies CHF, including bone wasting.

Purpose CHF with aldosteronism features a systemic illness that includes bone wasting. In rats with aldosteronism, secondary hyperparathyroidism (SHPT) with bone resorption has been observed and can be prevented by parathyroidectomy. SHPT may accompany human CHF as a result of aldosteronism and furosemide-enhanced urinary Ca2+ and Mg2+ excretion. We hypothesized SHPT in patients who were hospitalized for their CHF and where secondary aldosteronism would be expected. Methods Nine consecutive patients (7 males, 2 females; 8 African Americans, 1 Caucasian; 33-60 yrs of age) were hospitalized during a 28-day period (February 2005) with chronic left ventricular systolic dysfunction (EF < 35%) and CHF (NYHA Class III and IV) secondary to ischemic or idiopathic (dilated) cardiomyopathy. Five had clinical findings of decompensated failure and were untreated medically while 4 were similarly decompensated but treated with an ACE inhibitor, furosemide, and spironolactone. None of these 9 patients were receiving insulin, estrogen, a glucocorticoid, growth hormone, or thyroxine, and none had disorders affecting bone metabolism. Within 48 hours of admission, we monitored: serum parathyroid hormone (PTH); serum calcium corrected for albumin, magnesium, and phosphorus. Serum creatinine at the time of discharge was used to calculate creatinine clearance. Results Serum PTH was elevated (normal range 12-65 pg/mL) in both untreated (204 6 12 pg/mL) and treated (143 6 5 pg/mL) patients. Albumin-corrected serum calcium was within the normal range (8.4-10.2 mg/dL) in both untreated (9.7 6 0.1 mg/dL) and treated (9.1 6 0.2 mg/dL) patients as were serum magnesium (2.02 6 0.52 and 2.47 6 0.67 mg/dL) and phosphorus (3.5 6 0.1 and 4.2 6 0.3 mg/dL), respectively. Calculated creatinine clearance did not differ significantly between untreated (74 6 15 mL/min) and treated (83 6 21 mL/min) patients. Conclusions In predominantly African American patients, consecutively hospitalized with CHF during February 2005, SHPT was found in 5 untreated patients, where furosemide was not a consideration, and 4 medically treated patients. Corrected serum calcium was normal while serum-ionized calcium was not measured. Because we did not monitor 25(OH)D levels, we cannot exclude hypovitaminosis D in these housebound patients with CHF. SHPT may contribute to the systemic illness that accompanies CHF, including bone wasting.

A single infusion of pamidronate was given to patients with systemic sclerosis (scleroderma, SSc) to assess effects on cytokine production by peripheral blood mononuclear cells (PBMC) and lymphocyte subsets. Eighteen patients with SSc received a single intravenous dose of 60 mg of pamidronate and were followed for 6 months. Assessment of cytokine production [interferon (IFN)-gamma, interleukin (IL)-10, transforming growth factor (TGF)-beta 1, tumour necrosis factor (TNF)-alpha and IL-4] by PBMC and lymphocyte subsets by flow cytometry was carried out before and after the pamidronate infusion. Unstimulated PBMC produced increased amounts of IFN-gamma and TNF-alpha and reduced levels of TGF-beta 1 for up to 24 weeks after the infusion. gamma delta T cells from patients with SSc were activated in vitro and produced increased IFN-gamma. The effects of pamidronate on modulation of cytokine profiles in patients with SSc may merit future study.